Internet-delivered attentional bias modification training (iABMT) for the management of chronic musculoskeletal pain: a protocol for a randomised controlled trial

Introduction Chronic musculoskeletal pain is a complex medical condition that can significantly impact quality of life. Patients with chronic pain demonstrate attentional biases towards pain-related information. The therapeutic benefits of modifying attentional biases by implicitly training attention away from pain-related information towards neutral information have been supported in a small number of published studies. Limited research however has explored the efficacy of modifying pain-related biases via the internet. This protocol describes a randomised, double-blind, internet-delivered attentional bias modification intervention, aimed to evaluate the efficacy of the intervention on reducing pain interference. Secondary outcomes are pain intensity, state and trait anxiety, depression, pain-related fear, and sleep impairment. This study will also explore the effects of training intensity on these outcomes, along with participants’ perceptions about the therapy. Methods and analysis The study is a double-blind, randomised controlled trial with four arms exploring the efficacy of online attentional bias modification training versus placebo training theorised to offer no specific therapeutic benefit. Participants with chronic musculoskeletal pain will be randomised to one of four groups: (1) 10-session attentional modification group; (2) 10-session placebo training group; (3) 18-session attentional modification group; or (4) 18-session placebo training group. In the attentional modification groups, the probe-classification version of the visual-probe task will be used to implicitly train attention away from threatening information towards neutral information. Following the intervention, participants will complete a short interview exploring their perceptions about the online training. In addition, a subgroup analysis for participants aged 16–24 and 25–60 will be undertaken. Ethics and dissemination This study has been approved by the University of Southampton Research Ethics Committee. Results will be published in peer-reviewed journals, academic conferences, and in lay reports for pain charities and patient support groups. Trial registration number NCT02232100; Pre-results.

and sleep impairment. This study will also explore the effects of training intensity on these outcomes, along with participants' perceptions about the online therapy. Methods and analysis: The study is a double-blind randomised control trial with four arms exploring the efficacy of online attentional bias modification training versus placebo attentional control training theorised to offer no specific therapeutic benefit. Participants with chronic musculoskeletal pain will be randomised to one of four groups: (i) 10-session attentional modification group; (ii) 10-session attentional control group; (iii) 18-session attentional modification group; or (iv) 18-session attentional control group. In the attentional modification groups, the visual-probe task will be used to implicitly train attention away from threatening information towards neutral information.
Following the intervention, participants will complete a short interview exploring their perceptions about the online training. Data will be analysed and reported separately for participants aged 16 -24 and 25 -60. Ethics and dissemination: This study has been approved by the University of Southampton Research Ethics Committee. Results will be published in peerreviewed journals, academic conferences, and in lay reports for pain charities and patient support groups. Registration: The study protocol has been registered with ClinicalTrial.gov (NCT02232100).

Introduction
Chronic musculoskeletal pain (CMSK) is pain arising from bones, muscles, ligaments, tendons and/or joints lasting for more than three months. 1 Prevalence estimates of CMSK vary considerably, which for adults is estimated to affect between 11.4 and 24% of the population 2 and for children and adolescents ranges between 4 and 40% of the population. 3 Negative effects on quality of life are commonly reported in adult [4][5][6][7] and paediatric [8][9][10][11] CMSK populations, and theory driven research [12][13][14] has shown that patients with chronic pain exhibit attentional biases (i.e., a selective attention) for salient pain-related words (e.g., [15][16][17][18] ) and images (e.g., 19 20 ) relative to neutral information, particularly at longer stimuli presentation times (i.e., > 1000 ms) associated with maintained attention as indicated in meta-analyses. 21 22 Preliminary research has explored the effects of re-directing attention may have on pain and pain-related distress using attentional bias modification (ABM) techniques. ABM is a computer-based intervention which implicitly trains attention away from threat-related cues toward neutral information, and is frequently achieved through a modified version of the visual-probe task 23 ( Figure 1). Two small randomised controlled trials (RCTs) 24 25 and one pilot study 26 have used the modified visual-probe task to assess ABM in adults with chronic pain, which overall revealed statistically significant improvements in pain, disability and pain-related distress. One study reported clinically significant improvements in pain intensity, anxiety, depression and pain interference 26 , and another in and pain intensity. 25 One small RCT in adolescents with chronic pain reported no significant differences between ABM, placebo training and waiting-list groups on pain or painrelated outcomes. 27 Given the methodological shortcomings and small sample sizes of previous studies, further research conducted in real-world settings is needed to determine the therapeutic benefits of ABM for patients with chronic pain, along with the optimal form ABM should take and the impact of age on outcomes and intervention engagement.
This article presents a study protocol for a randomised, double-blind internet-delivered ABM intervention. The results of a pilot think aloud study informing the design of the intervention are also presented. The aim of this RCT is to assess the efficacy of internetdelivered ABM in improving pain and pain-related distress in people aged 16 -60 (considered separately in two age brackets [i.e., 16-24 and 25-60]) with CMSK. The primary outcome measures are pain intensity and pain interference. Secondary outcome measures are state and trait anxiety, depression, pain-related fear and sleep impairment, and engagement to and satisfaction with the online visual-probe training task. Dose effects will be explored via the inclusion of 10 versus 18 session conditions. It is hypothesised that participants in the intervention group, relative to those in the placebo group, will report significant reductions in pain intensity, pain interference, anxiety, depression, sleep impairment and pain-related fear at study endline. It is also hypothesised that dose will significantly moderate these findings, with greater effects in 18 compared to 10 sessions.

Participants
Participants will be recruited via press announcements, social media, and patient organizations throughout the UK. Inclusion criteria will be: (a) aged between 16 to 60 years old, (b) experiencing any type of CMSK (i.e., any condition that involves pain lasting for more than three months and arises from bones, muscles and/or joints), (c) able to sit at a personal computer for forty minutes, (d) normal or corrected to normal vision, (e) access to the internet at least twice a week, (f) access to, and familiarity using, a Windows-based computer, (g) successful completion of primary school, and (h) living in the United Kingdom. Exclusion criteria will be (1) experiencing malignant CMSK (i.e., pain caused due to a tumour), (2) a diagnosis of any psychiatric disorder, either currently or within the last 5 years, and (3) currently under psychiatric therapy. There are no restrictions placed on concomitant care and participants are not required to make any changes to current treatments they may be receiving. Patients will not be involved in recruitment of participants or conduct of the study. Results of this study will be disseminated to participants through presentation at consumer and community forums.

Study Design and Setting
The study is a double-blind randomised control trial (RCT) with four arms exploring the efficacy of online ABM training versus a placebo attentional control training theorised to offer no specific therapeutic benefits. The choice of comparator was selected as attentional control training closely mimics attentional bias modification training, and is frequently used as a comparator in ABM studies (e.g., 24 25 29 30 ). The study will take place in a location of the participants choice (which we anticipate will typically be their home), which is accessed via personal computer connected to the internet.
The study design has a 2 x 2 x 3 experimental structure, with multiple non-commensurate dependent variables measuring pain intensity and interference, emotional functioning and painrelated disability. ABM intervention is a two-level factor (10AMG and 18AMG), placebo control is a two-level factor (10ACG and 18ACG) with measures recorded at three points in time (baseline, endline, and 6-month follow-up). The study is powered primarily to establish treatment efficacy for the primary outcome variables of pain intensity and pain interference by considering baseline and endline measures between 10AMG and 10ACG. Randomisation should ensure baseline comparability on measures between these two groups, and a difference in beneficial outcomes between these groups will be modelled as a two-way interaction in the  will have in excess of 80% power (alpha = 0.05, beta = 0.13, non-centrality parameter lambda = 10). Data will be analysed and reported separately for participants aged 16 -24 and 25 -60.

Randomisation and Sample Size
Block randomisation of size four, performed via a randomisation command in the Lifeguide platform 31 , will be used to sequentially randomise consecutive consenting participants to one of four groups: (i) 10-session attentional modification group (10AMG); (ii) 10-session attentional control group (10ACG); (iii) 18-session attentional modification group (18AMG); or (iv) 18-session attentional control group (18ACG). An allocation concealment mechanism will be used to ensure neither participants nor researchers know the study group to which the next participant will be assigned. Participants randomised to either 10-session condition will receive ten 35-minute online sessions across a four-week period, while those randomised to either 18session condition will receive eighteen 35-minute online sessions across an eight-week period.
All online sessions will be administered twice a week on a separate set of days (Monday-Thursday, Tuesday-Friday). Participants randomised to either AMG condition will receive attentional training via the modified training version of the visual probe-task, while those randomised to either ACG condition will receive placebo training via the standard version of the visual-probe task. To maintain the overall quality and legitimacy of the intervention, code breaks (i.e., unbinding) will only occur in exceptional circumstances. Adherence will be monitored electronically via Lifeguide. We anticipate that a sample of 80 participants per age bracket i.e., 16-24 and 25-60 will afford the opportunity to robustly test the hypothesis, which is also considered feasible to recruit over a 2-year period.

Procedure
Interested individuals will be assessed against the inclusion and exclusion criteria via telephone interview. If eligible, they will receive a copy of the participant information sheet (PIS) detailing the requirements and procedure of the study, along with a link to the study website which provides further details on ABM and the research team. If the individual consents to take 8 part they will be required to create an online ABM account. During registration, participants will select their preferred days for training, which will be either (i) Monday/Thursday or (ii) Tuesday/Friday. Session 1 is the baseline session, and includes the first assessment visual-probe task assessing attentional biases prior to beginning the intervention, along with the questionnaire battery assessing the primary and secondary outcome measures. Randomisation will take place following session 1, where participants will be informed of the length of their training (i.e., four or eight weeks). Participants randomised to either of the ten session conditions will complete four pictorial and four linguistic training sessions, while those randomised to either of the 18 session conditions will complete eight pictorial and eight linguistic training sessions (baseline and endline assessment sessions comprise the remainder of the 10/18 sessions). Participants' attentional biases will be re-assessed at endline (i.e., during the final session 10/18) using the same assessment version of the visual probe task used at baseline and the same questionnaire battery. Participants' satisfaction with the online training will also be assessed. Six months after the last session, participants will be invited to again complete the online assessment visual-probe task and questionnaire battery. Within two weeks of the completion of the six-month follow-up session, participants will be invited to take part in a brief telephone semi-structured interview including 15 questions spread across five thematic sections: (a) motivation and expectations about the study, (b) experience of the online study -person, environmental and lifestyle parameters, (c) experience of the visual-probe task, (d) understanding of the process of change, and (e) the visual-probe task as a potential therapeutic tool in pain management. The study flow is presented in Table 1.
To retain as many participants as possible, reminder emails will be sent to participants 24 hours before each scheduled session becomes available, and also at 13:00 on the scheduled session date should the participant not have already logged into their iABMT account. An additional reminder email will be sent one week before their 6-month follow-up session is ready. Participants will also be sent encouragement emails informing them when they have reach specific milestones (i.e., successfully completing 5 sessions for those randomised to complete 10 sessions; successfully completing 6 and 12 sessions for those randomised to 18 sessions).
Participants will also have the option of receiving an SMS message on their mobile phone at 09:00 on the morning of each scheduled session.

The Intervention
The intervention will be hosted using LifeGuide and iSurvey platforms, both developed by the University of Southampton.
LifeGuide is an open-source software which allows researchers to create online interventions. 31 iSurvey is a survey generation tool which allows researchers to create and disseminate questionnaires online. Participants will register for the intervention using LifeGuide, which will also host the majority of the questionnaires. iSurvey will be used to host the visual-probe tasks, along with the Engagement with Online Training questionnaire and the Brief Pain Inventory 32 that appear at the end of every visual-probe task session. The flow of sessions is provided in Figure 2, and examples of webpages are shown in Guidance has been informed by research showing attention to be a limited capacity resource 33 34 , sleepiness to negatively influence concentration and performance 35 , alcohol to impair speed of information processing and cognition 36 , energy drinks to be associated with restlessness and nervousness 37 , caffeine to improves alertness 38 , large meals to be associated with impairments in cognitive functioning 39 , and hunger to influence patterns of attention. 40 41 Participants are provided with guidance to ensure concentration and comfort is maintained throughout each session: (1) allowing enough time for the session with no anticipated distractions, (2) adjusting screen brightness to match the brightness of the environment, (3) closing distracting applications such as Twitter and Facebook, (4) avoiding completing the session when tired, (5) not consuming alcohol at least 3 hours prior to the session, (6) caution in the use of energy drinks which may cause restlessness, (7) if the participant is a coffee or tea drinker, suggesting a cup 30 minutes prior to the session, and (8) avoiding completing the session when hungry or directly after a meal.
Visual-Probe Tasks. The flow of visual-probe sessions is illustrated in Figure 2. In total there will be eight linguistic and eight pictorial visual-probe training tasks used in the study, each with different stimuli. A complete description of the stimuli including ratings of valence, arousal, pain intensity, written frequency, and low-level features, is provided in Supplementary Material 1. A separate linguistic visual-probe task will be used in the three assessment sessions, featuring different stimuli to the linguistic training visual-probe tasks. The use of separate assessment and training stimuli is necessary to establish whether training effects generalise to novel stimuli not used in the actual training.
The ABM training version of the visual-probe task to be completed by AMG groups includes three main stages per trial ( Figure 1). Following a 500 ms initial fixation point, a stimulus pair are presented in distinct locations (e.g., above and below the initial fixation point) for either 500 or 1250 ms. The stimulus pair may be either words or images, although critically includes one threat-related and one neutral stimulus. 500 and 1250 ms presentation times are used to explore biases in initial orienting of attention and maintained attention respectively. 21 Immediately following their presentation, the stimuli disappear and a probe appears (i.e., either version of this paradigm completed by ACG groups and used in the assessment sessions, the probe replaces the neutral and threat-related stimulus an equal number of times.

Outcome Measures
The primary outcome measures of pain intensity and pain interference will be assessed by the Brief Pain Inventory -Short Form (BPI-SF 32  Training questionnaire (EOT). A demographic questionnaire developed by the researchers will be used at baseline to collect information on participants' age, gender, ethnicity, socio-economic status, place of residence, and pain characteristics. Aside from the SOT and EOT, questionnaires will be administered to participants at baseline, endline and at six-month follow-up. Full details on each outcome measure are provided in Supplementary Material 2.

Think Aloud Study
A qualitative think aloud study 28 including a short semi-structured interview was conducted following the development of the initial version with the aim to understand participants' first impressions and attitudes towards the intervention, and to collate feedback that could be used to make improvements. Details and outcomes of this study are provided in Supplementary Material 3.

Quantitative Analyses
Statistical analyses will be performed in IBM SPSS Statistics for Windows 24. For visual-probe data, and as per former research 19 26 , practice and incorrect trials will be removed prior to analyses. Box and whisker plots for overall data will be used to reveal overall outliers, which will be removed. Following this, mean response times will be computed for each participant, with any response >3SD from their individual mean also removed as outliers. This process ensures extremely quick or slow responses do not unduly bias the results, which are typically removed when cleaning and screening visual-probe data in pain-related research (e.g., 18 47 48 49 50 ). An attentional bias index will then be computed for each stimulus and presentation time condition using the following equation: (TuPl − TlPl)+(TlPu −TuPu))/2. Here T is the threatening stimulus, P is the probe, u is the upper position, and l is the lower position. The attention capturing quality of threatening stimuli is measured by subtracting the mean probe detection time for congruent trials from the mean probe detection time of incongruent trials. 21 Split-half reliability will be computed via a bootstrap procedure, by randomly splitting the total number of trials in two halves, such that each half has the same number of congruent and incongruent trials. Attentional bias scores will be computed for each half and the correlation between them calculated across participants. This procedure will be repeated 100 times, and an average split-half correlation computed. In order to determine any differences between participants who complete the study and those who do not, a series of independent sample t-tests will be conducted on questionnaire data collected at baseline (i.e., pain intensity, pain interference, anxiety, depression, pain-related fear, and sleeping impairment) and baseline attentional bias scores.
Considering completers only, a 2 (Time; baseline, endline) x 2 (Group; AMG, ACG) x 2 (Sessions; 10, 18) ANOVA will be conducted on attentional bias scores as a means to determine any training effect on such biases. The analyses of the primary (i.e., pain intensity and pain interference) and secondary outcome measures (i.e., state and trait anxiety, depression, painrelated fear, and sleep impairment) will also be conducted via a series of 2 (Time; baseline, endline) x 2 (Group; AMG, ACG) x 2 (Sessions; 10,18) ANOVAs. Of central interest to the study, these analyses will determine whether there are any differences between AMG and ACG groups at endline on patterns of attentional bias and outcome measures, and if so whether these depends on number of sessions (due to randomisation significant differences are not anticipated between groups at baseline). Further to these analyses, a series of 2 (Group; AMG, ACG) x 2 (Sessions; 10, 18) ANOVAs will be conducted on questions from the Satisfaction with the Online Training questionnaire, which will determine whether there are any differences between groups in their attitudes towards their online administered treatment. Finally, data from the Engagement with the Online Training questionnaire will be used to compute mean level of concentration per participant throughout the intervention, with the AMG and ACG groups compared via independent t-test.
ANOVAs and t-tests will be used where appropriate in post-hoc analyses to clarify significant main effects and interactions. For all analyses, the alpha level will be set at 0.05, 2tailed. For pairwise comparison analyses, Bonferonni correction will be applied to account for multiple comparisons. Correlations will be conducted in an exploratory manner between measures of attentional bias and the primary and secondary outcome measures, also with a Bonferonni correction applied due to the number of correlations made. In order to provide an unbiased estimate of the treatment effect 51 , the intention-to-treat principle will applied in these analyses; all randomised participants will be included in the analyses in the groups they were randomised to. Multiple imputation will be used in instances of missing data 52 53 . Similar to former studies 25 26 the Reliable Change Index (RCI) 54 will be used to assess primary and secondary outcome measures for clinically significant changes. Here, a clinically significant result is a post-treatment score falling outside two standard deviations of the mean population of interest (in this study, two standard deviations outside pre-treatment means). In contrast to tests of statistical significance comparing group means, tests of clinical significance explore effects of treatment on the individual. 55

Qualitative Analyses
Qualitative analysis will be used to detail participants' experiences completing the iABMT intervention. Specifically, thematic analysis using inductive encoding will be used to Guidelines provided by Braun and Clarke 56 will be followed. Following transcription of all interviews verbatim, initial codes will be generated. Potential themes and sub-themes will then be identified from the initial coding, which subsequently will be reviewed and refined. The validity of the themes in relation to the data set will also be considered. Each theme and subtheme will then be named and defined, and a thematic map of the data finalized. Examples from the data will be illustrated for each theme and sub-theme in the final report.

Ethics and Dissemination
This study has been approved by the University of Southampton Research Ethics Committee (ERGO ID: 26486), and the study protocol registered with ClinicalTrial.gov (NCT02232100). Ethical approval will be sought before any protocol modifications are made and the study protocol will be updated at ClinicalTrial.gov. Participants will provide informed consent prior to taking part in the study. All data will remain confidential and stored on password-protected systems and databases. Lifeguide and iSurvey servers both use HTTPS connections for security purposes. All data will be anonymised prior to dissemination, and personally identifiable information not known to anyone other than the researchers. Participants may withdraw from the intervention at any point by contacting the researchers via email or telephone, or by simply opting not to log into their iABMT account for their scheduled sessions.
Participants are also encouraged to contact the researchers should they experience any distress or discomfort completing the intervention. As per University policy, any harms or complaints arising from participation in the intervention will be reported to the University of Southampton Research Governance Office. Findings will be published in the most relevant, high-impact peerreviewed journals and presented at relevant conferences. Lay reports will be written for interested pain charities and patient support groups.        pictorial stimuli used in the visual-probe tasks. TG also assisted in programming the Lifeguide components. JZ was responsible for programming the visual-probe tasks to be used in the intervention, and assisted in programming the Lifeguide components. FH conducted the think aloud study. All authors contributed to the writing of this manuscript, and approve its final form.
These same authors will be included on future publications presenting intervention results.   Table 1. Schedule of enrolment, intervention, and assessments.

STUDY PERIOD Enrolment
Post-allocation TIMEPOINT** -t 1 t 1 X X X

FOP-III
X X X SOT X Interview X T1 = Baseline phase including standard assessment visual-probe task and questionnaires. Also includes randomization to groups. T2 = Training phase including training visual-probe tasks. T3 = Evaluation phase including standard assessment visual-probe task and questionnaires. T4 = Six-month follow-up including standard assessment visual-probe task and questionnaires. T5 = Telephone interview within two weeks of T4.

Stimuli Development and Properties
A detailed description of the stimuli to be used in the iAMBT intervention is presented in this document. Linguistic stimulus properties and analyses on written frequency, valence, and arousal are first presented, followed by a description of pictorial stimuli properties and analyses of low-level features, valence, arousal and pain intensity. Following this, comparisons of stimuli properties between visual-probe sessions are then presented for linguistic and pictorial stimuli.

Linguistic stimuli
Properties. Linguistic and pictorial versions of the visual-probe task will be used. Each linguistic visual-probe task will include 32 threatening/neutral and 16 neutral/neutral word pairs.
Threatening words stem from the following categories, with 8 words from each included in each visual-probe task: (i) sensory-pain words reflecting the sensory dimension of pain (e.g., shooting; burning; aching); (ii) affective-pain words reflecting the unpleasantness of pain and negative emotions associated with pain (e.g., hopeless, punishing, tormenting); (iii) health-threat words reflecting threat to health and well-being (e.g., hospital, doctor, stress); and (iv) general-threat words reflecting physical and emotional sources of threat, including manmade threat (e.g., gun), natural threat (e.g., fire), social threat (e.g., humiliation), and emotional threat (e.g., sad). Neutral words (including the neutral counterparts of the threatening words) include non-threatening words unrelated to pain or suffering (e.g., version; rector; monument), which were matched with their threatening counterparts on Kucera-Francis written frequency of use in the English language 1 and word length. Matching on written frequency minimise the chances of participants preferentially processing one stimulus due to its high frequency of use (e.g., faster recognition) when displayed simultaneously with another stimulus 2 3 , while matching word length also minimise the chances of participants attending towards a stimulus due to its size.
In total, 864 words have been collected from previous studies exploring and modifying biases in pain and/or anxiety (i.e., [4][5][6][7][8], including words from the McGill Pain Questionnaire. 9 Matching of threatening and neutral words was achieved via the MRC Psycholinguistic database 10 , an online psycholinguistic tool that generates words with specific lexical characteristics. The database includes a dictionary of 150,837 English words providing syntactic, semantic and orthographical properties of each word. 11 Valence and arousal can influence attentional allocation to external stimuli. 12 13 A computerised version of the SAM task 14 was therefore used to collect ratings on valence and arousal for each word in a sample of sixteen healthy, pain-free participants (M age = 25.9, SD = 4.08, range: 20 -33 years; 8 female). All words were randomly presented to participants for 3 seconds each. Following each word, two 9point SAM scales were presented, one for valence (1 = low pleasure to 9 = high pleasure) and one for arousal (1 = low arousal to 9 = high arousal). As per former chronic pain attentional bias research (e.g., 5 15 16 ), stimuli categories were assessed but not matched on valence and arousal, as differences are expected to exist between categories.
Analyses and results: written frequency, valence, and arousal. Analyses comparing properties between the five word categories are presented here, while analyses comparing word properties between the nine linguistic visual-probe tasks are presented below. One-way ANOVA was conducted comparing Kucera-Francis written frequency (Table 1) across words in the five word categories, revealing no significant main effect, F(4, 853) = 1.97, p = . 10.
A repeated-measures ANOVA was conducted comparing arousal ratings (Table 2) Table 1 Mean Kucera-Francis Written Frequency per Word Category

Pictorial Stimuli
Properties. Pictorial visual-probe tasks each include 32 threatening/neutral and 16 neutral/neutral image pairs. Threatening images stem from the following categories: (i) musculoskeletal pain images depicting people experiencing pain in muscles and/or joints, including images of people performing daily activities that can be considered painful and/or harmful for individuals with CMP (e.g., a person running; a person lifting a heavy weight with poor posture); (ii) facial expressions of pain, featuring a single model depicting a prototypical pain expression -closing the eyes or narrowing the eyelids, lowering the eyebrows, wrinkling the nose or raising the cheek, and partly opening the mouth or extending the lips 17 , including horizontal lip stretching and/or oblique lip raising 18 ; (iii) health-threat images reflecting threat to health and well-being (e.g., medication, wheelchair); and (iv) general-threat images reflecting physical and emotional sources of threat, including manmade threat (e.g., gun), natural threat (e.g., flood), and social threat (e.g., social isolation). Neutral images (including the neutral pairs of the threatening images) depict non-threatening objects (e.g., a car) and people performing every-day activities (e.g., a person reading a newspaper). In total, 768 images have been collected from previous studies exploring and modifying attentional biases in chronic pain (i.e., 5 19 ), including online databases providing batteries of pictorial stimuli for research (i.e., International Affective Picture System database 20   An independent samples t-test was conducted comparing pain intensity scores (Table 4) between the images in the musculoskeletal pain and facial expressions of pain categories. There

Supplementary Material 2 -Outcome Measures
A detailed description of each outcome measure used in this study is provided here.
While the questionnaires will be administered online as part of this study, the psychometric properties reported are for paper and pencil versions of the questionnaires.
The BPI-SF 1 is a commonly used measure of pain intensity and pain interference.  The FOP-III 8 is a 30 item measure of pain-related fear. On a 5-point scale, respondents are asked to rate how fearful they are of pain associated with specific situations and events (e.g., being in an automobile accident). Possible scores range between 30 and 150, with higher scores representing a more intense fear of pain. In addition to a total score, the measure also provides subscales of minor, severe, and medical pain-related fear. The FOP-III is commonly used in clinical and non-clinical populations, and possesses high internal consistency as indexed in a nonclinical sample (total score = .93; severe = .88; minor = .86, medical = .88). 9 The MOS-SS 10 is a twelve-item questionnaire developed for patients with chronic illness, measuring six dimensions of sleep over the past four weeks; sleep initiation (time to fall asleep), quantity (hours per night sleeping), maintenance, respiratory problems, perceived adequacy, and somnolence. A sleep problems index which summarises information from nine items may also be scored. Responses are recoded on a 0 -100 scale, with higher scores indicating more of the concept being measured (e.g., greater difficulties falling asleep). Research has supported the internal consistency of the MOS-SS scales to be acceptable (.70) or higher in samples of patients with neuropathic pain. 11 12 The SOT 13 assesses participants' attitudes towards their online administered treatment, and will be used at the study endline. Participants state how strongly they agree/disagree with each of the following items: (a) the use of a computer to access treatment, (b) level of easiness of the online intervention, (c) duration of the potential effects of the treatment, and (d) potential recommendation of online interventions to others. Responses range from "Agree very strongly" to "Disagree very strongly". An additional question asks participants how helpful they have found the online intervention, with responses ranging from "Very helpful" to "Not at all helpful".
Two open questions are also included that require participants to state the aspects of the intervention they most liked and disliked.
The EOT, developed by the researchers, will be presented at the end of every online session. The EOT includes three questions. The first asks participants to indicate where they

Supplementary Material 3 -Think Aloud Study
A qualitative think aloud study 1  Following the think-aloud interview, a short semi-structured interview took place for the researcher to ask questions about any specific aspects of the intervention that had not yet been discussed. Questions were also asked regarding thoughts about the intervention as a whole. This method of triangulation is commonly used to complement a think-aloud interview because it can be difficult to interpret spoken thoughts alone. 4 5 Following transcription of the interviews, thematic analysis using inductive encoding was used to identify themes that clearly represent the raw data, following guidelines set out by Braun and Clarke. 6 Three themes and 13 subthemes were identified, which are shown in a thematic map in Figure S1 and defined in Table S1 below. While it is beyond the scope of this article to present the results of this thematic analysis in full, the main points resulting in amendments to the iABMT intervention are presented here.
Regarding the iABMT website, participants liked the continuity of design between webpages, although pointed out inconsistencies in the formatting of text, which have been rectified. On some pages the volume of text was considered to be too great, and therefore where possible text has been reduced, language simplified, better use of spacing made, and longer paragraphs divided into multiple shorter paragraphs. While some participants were positive about the inclusion of images, others felt additional visual stimuli could be added throughout. It was therefore decided to only include images where these would help emphasize the points being made. Regarding the visual-probe task sessions, one important practicality raised was ability of participants to stay seated for a sufficient amount of time in order to complete the task in a single session. An additional inclusion criteria has therefore been added to the study, being that participants must be able to sit at a personal computer for forty minutes. It was also mentioned that participants needed sufficient computer skills to take part in the study. The inclusion criteria were therefore amended to state that participants need both access to and familiarity using a Window-based computer. impairment. This study will also explore the effects of training intensity on these outcomes, along with participants' perceptions about the online therapy. Methods and analysis: The study is a double-blind randomised controlled trial with four arms exploring the efficacy of online attentional bias modification training versus placebo training theorised to offer no specific therapeutic benefit. Participants with chronic musculoskeletal pain will be randomised to one of four groups: (i) 10-session attentional modification group; (ii) 10-session placebo training group; (iii) 18-session attentional modification group; or (iv) 18-session placebo training group. In the attentional modification groups, the visual-probe task will be used to implicitly train attention away from threatening information towards neutral information. Following the intervention, participants will complete a short interview exploring their perceptions about the online training.
In addition, data will be analysed and reported separately for participants aged 16 -24 and 25 -60. Ethics and dissemination: This study has been approved by the University of Southampton Research Ethics Committee. Results will be published in peer-reviewed journals, academic conferences, and in lay reports for pain charities and patient support groups. Registration: The study protocol has been registered with ClinicalTrial.gov (NCT02232100).

Strengths and limitations of this study
 This protocol describes an internet-delivered intervention to explore the efficacy of attentional bias modification training in patients with chronic musculoskeletal pain.
 Recruitment of a diverse sample in terms of age, socioeconomic status, and geographical region.
 Results will provide important information regarding dose effects, age effects and participants' experiences and attitudes using the online intervention.
 Limited control over the conditions under which training is completed.
 Impossibility of independently verifying participant diagnosis.

Introduction
Chronic musculoskeletal pain (CMSK) is pain arising from bones, muscles, ligaments, tendons and/or joints lasting for more than three months. 1 Prevalence estimates of CMSK vary considerably, which for adults is estimated to affect between 11.4 and 24% of the population 2 and for children and adolescents ranges between 4 and 40% of the population. 3 Negative effects on quality of life are commonly reported in adult 4-7 and paediatric [8][9][10][11] CMSK populations, and theory driven research [12][13][14] has shown that patients with chronic pain exhibit attentional biases (i.e., a selective attention) for salient pain-related words (e.g., [15][16][17][18] ) and images (e.g., 19 20 ) relative to neutral information. Three meta-analyses have supported the presence of attentional biases in chronic pain patients [21][22][23] , although evidence for the time course of such biases is mixed.
Specifically, two meta-analyses reported larger effect sizes when stimuli are presented for longer than 1000 ms, 24 25 whereas a recent analysis found evidence of bias for presentation times of 500 -1000ms but not when stimuli are presented for longer than 1000 ms. 23 Despite this inconsistency attentional biases are commonly shown in chronic pain, and preliminary research has explored the effects of re-directing attention may have on pain and pain-related distress using attentional bias modification (ABM) techniques. ABM is a computer-based intervention which implicitly trains attention away from threat-related cues toward neutral information, and is frequently achieved through a modified version of the visual-probe task 26 ( Figure 1).
Two small randomised controlled trials (RCTs) 27 28 and one pilot study 29 have used the modified visual-probe task to assess ABM in adults with chronic pain. Carleton and colleagues 30 found participants receiving ABM showed significant reductions pre-to post ABM in anxiety sensitivity and fear of pain, and marginally significant reduction in current pain severity. No significant reductions were found in illness/injury sensitivity or pain anxiety. Significantly more patients receiving ABM reported clinically significant change in current pain compared with those in the placebo group (44% vs. 17%, respectively). Attentional bias scores were not recorded, and therefore the researchers could not comment on mechanisms of action. Sharpe and were found for pain, fear of pain, fear of re-injury, depression, anxiety, stress, anxiety sensitivity or pain self-efficacy. At 6-month follow-up (and after all participants had undergone 8 sessions of CBT) the ABM group, compared to the placebo group, showed significant improvements in disability and anxiety sensitivity, and marginally significant improvements in fear of re-injury.
No other significant effects were found, and the mechanism of action could not be established as ABM was not found to change patterns of attentional bias across time Schoth and colleagues 29 reported statistically and clinically significant change pre-to post-ABM in pain intensity, pain interference, anxiety, and depression. Assessed via the McGill Pain Questionnaire 32 , significant changes pre-to post-ABM were shown for total pain, affective pain and miscellaneous pain, but not sensory-pain or evaluative pain. There was also no evidence that attentional biases changed across time.
One small RCT in adolescents with chronic pain randomised participants to either ABM, placebo training or waiting-list groups. No significant differences were found between the three groups in terms of pain, disability pain catastrophising, anxiety, depression, or objective measures of physical functioning (sit-to-stand task and cardio wall tasks), and no evidence was found that ABM changed attentional bias or attentional control compared to placebo and waitinglist conditions. 33 Overall, while some studies have provided support for the benefits of ABM in adults, the evidence in regards to specific outcome variables is mixed and the mechanisms of action have yet to be established. Given the methodological shortcomings and small sample sizes of previous studies however, further research is needed to determine the therapeutic benefits of ABM for patients with chronic pain, along with the optimal form ABM should take and the impact of age on outcomes and intervention engagement.
This article presents a study protocol for a randomised, double-blind internet-delivered ABM intervention. The results of a pilot think aloud study informing the design of the depression, pain-related fear and sleep impairment, and engagement to and satisfaction with the online visual-probe training task. Dose effects will be explored via the inclusion of 10 versus 18 session conditions. It is hypothesised that participants in the intervention group, relative to those in the placebo group, will report significant reductions in pain intensity, pain interference, anxiety, depression, sleep impairment and pain-related fear at study endline. It is also hypothesised that dose will significantly moderate these findings, with greater effects in 18 compared to 10 sessions.

Participants
Participants will be recruited via press announcements, social media, and patient organizations throughout the UK. Inclusion criteria will be: (a) aged between 16 to 60 years old, (b) experiencing any type of CMSK (i.e., any condition that involves pain lasting for more than three months and arises from bones, muscles and/or joints), (c) able to sit at a personal computer for forty minutes, (d) normal or corrected to normal vision, (e) access to the internet at least twice a week, (f) access to, and familiarity using, a Windows-based computer, (g) successful completion of primary school, and (h) living in the United Kingdom. Exclusion criteria will be (1) experiencing malignant CMSK (i.e., pain caused due to a tumour), (2) a diagnosis of other forms of comorbid chronic pain (e.g., chronic headache), and (3) a diagnosis of any psychiatric disorder, either currently or within the last 5 years. There are no restrictions placed on concomitant care and participants are not required to make any changes to current treatments they may be receiving.

Patient and Public Involvement
Participant burden of the intervention and research measures were assessed using individual interviews and informal feedback from patients participating in two pilot studies. 29 34 Patients will not be involved in recruitment of participants or conduct of the study. Results of this study will be disseminated to participants through presentation at client and community forums.

Study Design and Setting
The study is a double-blind randomised controlled trial (RCT) with four arms exploring the efficacy of online ABM training versus a placebo training condition theorised to offer no specific therapeutic benefits. The choice of comparator was selected as placebo training closely mimics attentional bias modification training, and is frequently used as a comparator in ABM studies (e.g., 27 28 35 36 ). The study will take place in a location of the participants choice (which we anticipate will typically be their home), which is accessed via personal computer connected to the internet.
The study design has a 2 x 2 x 3 experimental structure, with multiple non-commensurate dependent variables measuring pain intensity and interference, emotional functioning and painrelated disability. ABM intervention is a two-level factor (10AMG and 18AMG), placebo control is a two-level factor (10PCG and 18PTG) with measures recorded at three points in time (baseline, endline, and 6-month follow-up). Measures in the 18 session groups (18AMG and 18 PTG) will also be taken after session 10.

Randomisation and Sample Size
Block randomisation of size four, performed via a randomisation command in the Lifeguide platform 37 , will be used to sequentially randomise consecutive consenting participants to one of four groups: (i) 10-session attentional modification group (10AMG); (ii) 10-session 18-session placebo training group (18PTG). This blocked randomisation will be performed separately for those aged 16-24 and those aged 25-60. An allocation concealment mechanism will be used to ensure neither participants nor researchers know the study group to which the next participant will be assigned. This will be automatically performed within the Lifeguide platform (see below), with participants provided access to appropriate AMG or PTG sessions. Participants randomised to either 10-session condition will receive ten 35-minute online sessions across a four-week period, while those randomised to either 18-session condition will receive eighteen 35minute online sessions across an eight-week period. All online sessions will be administered twice a week on a separate set of days (Monday-Thursday, Tuesday-Friday). Participants randomised to either AMG condition will receive attentional training via the modified training version of the visual probe-task, while those randomised to either PTG condition will receive placebo training via the standard version of the visual-probe task. To maintain the overall quality and legitimacy of the intervention, code breaks (i.e., unblinding) will only occur in exceptional circumstances. Adherence will be monitored electronically via Lifeguide.
This study is powered primarily to establish treatment efficacy for the primary outcome variables of pain intensity and pain interference by considering baseline and endline measures between 10AMG and 10PTG. Randomisation should ensure baseline comparability on measures between these two groups, and a difference in beneficial outcomes between these groups will be modelled using a linear mixed model. For an assumed correlation of 0.7 between baseline and endline a total of n = 20 per group would be needed to detect medium sized intervention differences with at least 80% power (alpha = 0.05, two-sided). Under the same conditions a sample size of n = 40 per group would have in excess of 80% power to effects (Cohen's d = 0.25). A 20% oversampling will be undertaken to mitigate a loss of power from loss to followup. Our former lab-based proof-of-concept ABM intervention found reductions in pain intensity and pain interference reduction pre-to post-ABM were associated with large effect sizes 29 , although differences in methodology including delivery (online vs lab-based) and number of sessions warrants a more conservative estimate.

Procedure
Interested individuals will contact the researchers on the details provided in study advertisements and will be assessed against the inclusion and exclusion criteria via telephone interview. If eligible, they will receive a copy of the participant information sheet (PIS) detailing the requirements and procedure of the study, along with a link to the study website which provides further details on ABM and the research team. If the individual consents to take part they will be required to create an online ABM account. During registration, participants will select their preferred days for training, which will be either (i) Monday/Thursday or (ii) Tuesday/Friday. Session 1 is the baseline session, and includes the first assessment visual-probe task assessing attentional biases prior to beginning the intervention, along with the questionnaire battery assessing the primary and secondary outcome measures. Randomisation will take place following session 1, where participants will be informed of the length of their training (i.e., four or eight weeks). Participants randomised to either of the ten session conditions will complete four pictorial and four linguistic training sessions, while those randomised to either of the 18 session conditions will complete eight pictorial and eight linguistic training sessions (baseline and endline assessment sessions comprise the remainder of the 10/18 sessions). Participants' attentional biases will be re-assessed at endline (i.e., during the final session 10/18) using the same assessment version of the visual probe task (i.e., featuring the same stimuli) used at baseline and the same questionnaire battery. Participants randomised to either of the 18 session conditions will also have their attentional biases re-assessed in session 10 after their training session.
Participants' satisfaction with the online training will also be assessed. Six months after the last session, participants will be invited to again complete the online assessment visual-probe task (same as baseline and final session 10/18) and questionnaire battery. Within two weeks of the completion of the six-month follow-up session, participants will be invited to take part in a brief telephone semi-structured interview including 15 questions spread across five thematic sections: (a) motivation and expectations about the study, (b) experience of the online studyperson, environmental and lifestyle parameters, (c) experience of the visual-probe task, (d) understanding of the process of change, and (e) the visual-probe task as a potential therapeutic tool in pain management. The study flow is presented in Table 1.

INTERVENTIONS:
Attentional bias modification training X ASSESSMENTS: Demographic questionnaire = Baseline phase including standard assessment visual-probe task and questionnaires. Also includes randomization to groups. T2 = Training phase including training visual-probe tasks. T3 = Evaluation phase including standard assessment visual-probe task and questionnaires. To retain as many participants as possible, reminder emails will be sent to participants 24 hours before each scheduled session becomes available, and also at 13:00 on the scheduled session date should the participant not have already logged into their ABMT account. An additional reminder email will be sent one week before their 6-month follow-up session is ready.
Participants will also be sent encouragement emails informing them when they have reach specific milestones (i.e., successfully completing 5 sessions for those randomised to complete 10 sessions; successfully completing 6 and 12 sessions for those randomised to 18 sessions).
Participants will also have the option of receiving an SMS message on their mobile phone at 09:00 on the morning of each scheduled session.

The Intervention
The intervention will be hosted using LifeGuide and iSurvey platforms, both developed by the University of Southampton.
LifeGuide is an open-source software which allows researchers to create online interventions. 37 iSurvey is a survey generation tool which allows researchers to create and disseminate questionnaires online. Participants will register for the intervention using LifeGuide, which will also host the majority of the questionnaires. iSurvey will be used to host the visual-probe tasks, along with the Engagement with Online Training questionnaire and the Brief Pain Inventory 38 that appear at the end of every visual-probe task session. The flow of sessions is provided in Figure 2, and examples of webpages are shown in Figure 3. On loading the intervention homepage, the individual is provided with a brief welcome to the website and rationale for the intervention. A recent review of cognitive bias meta-analyses concluded that effect sizes were smaller when biases were modified remotely compared to laboratory-based training. 39 We therefore decided to provide information on the rationale behind ABMT in order to increase motivation and reduce attrition as much as possible, which also mirrors clinical practice that involves educating patients into chronic pain and the psychological interventions used in its management. Individuals are able to either create an iABMT account or log into their existing account. Before any session participants are asked to indicate whether they  1. To briefly summarise, each linguistic visual-probe task includes 32 threatening/neutral and 16 neutral/neutral word pairs. Each task includes eight threatening words from each of the following categories: sensory-pain, affective-pain, health-threat and general-threat. Each pictorial task includes 32 threatening/neutral and 16 neutral/neutral image pairs. Each task includes eight threatening images from the following categories: musculoskeletal pain, facial expressions of pain, health-threat and general-threat. A total of 384 trials are included in each task, with each stimuli-pair presented four times for 500 ms and four times for 1250 ms. Within each exposure duration, each stimulus appears twice in the upper location of the screen, and twice in the lower location.
A separate linguistic visual-probe task will be used in the three assessment sessions, featuring different stimuli to the linguistic training visual-probe tasks. The use of separate assessment and training stimuli is necessary to establish whether training effects generalise to novel stimuli not used in the actual training. The same assessment stimuli will be used in all assessment sessions. The ABM training version of the visual-probe task to be completed by AMG groups includes three main stages per trial ( Figure 1). Following a 500 ms initial fixation point, a stimulus pair are presented in distinct locations (e.g., above and below the initial fixation point) for either 500 or 1250 ms. The stimulus pair may be either words or images, although critically includes one threat-related and one neutral stimulus. 500 and 1250 ms stimuli presentation times are used as these are the most common stimuli presentation times adopted in chronic pain visual-probe studies (e.g., 18 49 50 ), and will allow us to closely compare our results to those of former research. Immediately following their presentation, the stimuli disappear and a probe appears (i.e., either 'p' or 'q') in the location of the neutral stimulus. Participants indicate the location of the probe as quickly and as accurately as possible via corresponding keys on their keyboard. In the standard version of this paradigm completed by PTG groups and used in the assessment sessions, the probe replaces the neutral and threat-related stimulus an equal number of times.

Outcome Measures
The primary outcome measures of pain intensity and pain interference will be assessed by the Brief Pain Inventory -Short Form (BPI-SF 38  Training questionnaire (EOT). A demographic questionnaire developed by the researchers will be used at baseline to collect information on participants' age, gender, ethnicity, socio-economic status, place of residence, and pain characteristics. Aside from the SOT and EOT, questionnaires in the 10 session groups (10AMG and 10PTG) will be administered to participants at baseline, after 10 sessions, and at six-month follow-up. In the 18 session groups (18AMG and 18PTG) questionnaires will be administered to participants at baseline, after 10 sessions, after 18 sessions, and at six-month follow-up. At endline for each participant we will also assess whether the participant and researchers became aware at any point prior to endline which group they had been allocated to. Full details on each outcome measure are provided in Supplementary Material 2.

Think Aloud Study
A qualitative think aloud study 34 including a short semi-structured interview was conducted following the development of the initial version with the aim to understand participants' first impressions and attitudes towards the intervention, and to collate feedback that could be used to make improvements. Details and outcomes of this study are provided in Supplementary Material 3. A full and detailed Statistical Analysis Plan will be written prior to trial closure. In brief, the data analysis will be performed on an intention-to-treat (ITT) basis to provide an unbiased estimate of the treatment effect. 56 Per protocol analyses will also be performed (comprising those correctly randomized, without protocol violations, and providing complete data on the primary outcome measure). A linear mixed model with random intercepts will be used to analyze the data. This approach avoids listwise deletion which would apply in a repeated measures ANOVA approach. The linear mixed modelling approach uses all of the available data, and adheres to ITT. As a sensitivity analysis we will used multiple imputation chained equations (MICE) to impute outcome data 57 58 and uses these imputed data sets in the linear mixed model. Pairwise comparisons will follow the same procedure. The analysis plan would apply to the primary (i.e., pain intensity and pain interference) and secondary outcome measures. Similar to former studies 28 29 the Reliable Change Index (RCI) 59 will be used to assess primary and secondary outcome measures for changes over and above changes which could otherwise be attributed to measurement unreliability. Here, the minimum clinically significant result occurs if the posttreatment score differs from the pre-treatment score by the minimum detectable difference at the 95% level (i.e. by 2 standard deviations). In contrast to tests of statistical significance comparing group means, an assessment of the RCI is an exploration of effects of the treatment on the individual. 60 For visual-probe data, and as per former research 19 29 , practice and incorrect trials will be removed prior to analyses. Box and whisker plots for overall data will be used to reveal overall outliers, which will be removed. Following this, mean response times will be computed for each participant, with any response >3SD from their individual mean also removed as outliers. This process ensures extremely quick or slow responses do not unduly bias the results, which are typically removed when cleaning and screening visual-probe data in pain-related research (e.g., 18 61 62 63 64 ). An attentional bias index will then be computed for each stimulus and presentation time condition using the following equation: (TuPl − TlPl)+(TlPu −TuPu))/2. Here T is the threatening stimulus, P is the probe, u is the upper position, and l is the lower position. The attention capturing quality of threatening stimuli is measured by subtracting the mean probe detection time for congruent trials from the mean probe detection time of incongruent trials. 21 Split-half reliability will be computed via a bootstrap procedure, by randomly splitting the total number of trials in two halves, such that each half has the same number of congruent and incongruent trials. Attentional bias scores will be computed for each half and the correlation between them calculated across participants. This procedure will be repeated 100 times, and an average split-half correlation computed

Qualitative Analyses
Qualitative analysis will be used to detail participants' experiences completing the ABMT intervention. Specifically, thematic analysis using inductive coding will be used to identify themes present in the data obtained from the semi-structured interviews and the two open-ended questions included in the Satisfaction with the Online Training questionnaire. Guidelines provided by Braun and Clarke 65 will be followed. Following transcription of all interviews verbatim, initial codes will be generated. Potential themes and sub-themes will then be identified from the initial coding, which subsequently will be reviewed and refined. The validity of the themes in relation to the data set will also be considered. Each theme and sub-theme will then be named and defined, and a thematic map of the data finalized. Examples from the data will be illustrated for each theme and sub-theme in the final report.

Ethics and Dissemination
This study has been approved by the University of Southampton Research Ethics Committee (ERGO ID: 26486), and the study protocol registered with ClinicalTrial.gov (NCT02232100). Ethical approval will be sought before any protocol modifications are made and the study protocol will be updated at ClinicalTrial.gov. Participants will provide informed consent prior to taking part in the study. All data will remain confidential and stored on password-protected systems and databases. Lifeguide and iSurvey servers both use HTTPS connections for security purposes. All data will be anonymised prior to dissemination, and personally identifiable information not known to anyone other than the researchers. Participants may withdraw from the intervention at any point by contacting the researchers via email or telephone, or by simply opting not to log into their iABMT account for their scheduled sessions.
Participants are also encouraged to contact the researchers should they experience any distress or discomfort completing the intervention. As per University policy, any adverse events, harms or complaints arising from participation in the intervention will be reported to the University of Southampton Research Governance Office. Findings will be published in the most relevant, high-impact peer-reviewed journals and presented at relevant conferences. Lay reports will be written for interested pain charities and patient support groups.                Linguistic visual-probe task

Stimuli Development and Properties
A detailed description of the stimuli to be used in the iAMBT intervention is presented in this document. Linguistic stimulus properties and analyses on written frequency, valence, and arousal are first presented, followed by a description of pictorial stimuli properties and analyses of low-level features, valence, arousal and pain intensity. Following this, comparisons of stimuli properties between visual-probe sessions are then presented for linguistic and pictorial stimuli.

Linguistic stimuli
Properties. Linguistic and pictorial versions of the visual-probe task will be used. Each linguistic visual-probe task will include 32 threatening/neutral and 16 neutral/neutral word pairs.
Threatening words stem from the following categories, with 8 words from each included in each visual-probe task: (i) sensory-pain words reflecting the sensory dimension of pain (e.g., shooting; burning; aching); (ii) affective-pain words reflecting the unpleasantness of pain and negative emotions associated with pain (e.g., hopeless, punishing, tormenting); (iii) health-threat words reflecting threat to health and well-being (e.g., hospital, doctor, stress); and (iv) general-threat words reflecting physical and emotional sources of threat, including manmade threat (e.g., gun), natural threat (e.g., fire), social threat (e.g., humiliation), and emotional threat (e.g., sad). Neutral words (including the neutral counterparts of the threatening words) include non-threatening words unrelated to pain or suffering (e.g., version; rector; monument), which were matched with their threatening counterparts on Kucera-Francis written frequency of use in the English language 1 and word length. Matching on written frequency minimise the chances of participants preferentially processing one stimulus due to its high frequency of use (e.g., faster recognition) when displayed simultaneously with another stimulus 2 3 , while matching word length also minimise the chances of participants attending towards a stimulus due to its size.
In total, 864 words have been collected from previous studies exploring and modifying biases in pain and/or anxiety (i.e., [4][5][6][7][8]  Matching of threatening and neutral words was achieved via the MRC Psycholinguistic database 10 , an online psycholinguistic tool that generates words with specific lexical characteristics. The database includes a dictionary of 150,837 English words providing syntactic, semantic and orthographical properties of each word. 11 Valence and arousal can influence attentional allocation to external stimuli. 12 13 A computerised version of the SAM task 14 was therefore used to collect ratings on valence and arousal for each word in a sample of sixteen healthy, pain-free participants (Mage = 25.9, SD = 4.08, range: 20 -33 years; 8 female). All words were randomly presented to participants for 3 seconds each. Following each word, two 9point SAM scales were presented, one for valence (1 = low pleasure to 9 = high pleasure) and one for arousal (1 = low arousal to 9 = high arousal). As per former chronic pain attentional bias research (e.g., 5 15 16 ), stimuli categories were assessed but not matched on valence and arousal, as differences are expected to exist between categories.

Analyses and results: written frequency, valence, and arousal. Analyses comparing
properties between the five word categories are presented here, while analyses comparing word properties between the nine linguistic visual-probe tasks are presented below. One-way ANOVA was conducted comparing Kucera-Francis written frequency (Table 1) across words in the five word categories, revealing no significant main effect, F(4, 853) = 1.97, p = .10.
A repeated-measures ANOVA was conducted comparing arousal ratings (   This rating aimed to assess the degree to which images included in the pain-related categories were perceived as depicting pain. Sixteen healthy, pain-free participants (Mage = 24.8, SD = 4.56, range: 20 -33 years; 8 female) were recruited to provide ratings on valence, arousal, and pain intensity (this was a separate sample to that recruited to provide linguistic stimuli ratings).
Analyses and results: Low-level features. Analyses comparing properties between the five image categories on low-level features (Table 3) are presented here, while analyses  An independent samples t-test was conducted comparing pain intensity scores (Table 4) between the images in the musculoskeletal pain and facial expressions of pain categories. There   Comparison between Visual-Probe Sessions -Linguistic Stimuli

Post-hoc analyses across sessions.
To explore the significant interaction, a series of oneway ANOVAS with 9 levels (Session; 1, 3,5,7,9,11,13,15,17) were run for each word category independently. These explored whether the pleasantness ratings for each word category differed across the sessions. For the sensory-pain words, a main effect of session was found,   For session 9, a significant main effect was found, F(2,31) = 13.67, p < .001, p 2 = .48.
Pairwise comparisons revealed that the sensory-pain words were significantly more pleasant than For session 11, a significant main effect was found, F(3,45) = 11.63, p < .001, p 2 = .44.
Pairwise comparisons revealed that the sensory-pain words were significantly more pleasant than

Post-hoc analyses within image categories.
To explore the significant interaction, a series of one-way ANOVAs with 8 levels (Session; 2 Post-hoc analyses within sessions. To further explore the significant interaction, a series of one-way ANOVAs with 4 levels (image category; musculoskeletal-pain, facial expressions of pain, general-threat and health-threat) were conducted for each session independently. These   The images in general-threat categories were significantly more arousing that those included in the health-threat category (Md = 1.00, SE = 0.20, p = .001).
A significant main effect of image category was found in session 10     For session 6, a significant main effect was found, F(3,45) = 32.12, p <.001, p 2 = .68.
Pairwise comparisons revealed that images in the musculoskeletal-pain category were       For the general-threat category, a significant interaction for session number was found,

Supplementary Material 2 -Outcome Measures
A detailed description of each outcome measure used in this study is provided here.
While the questionnaires will be administered online as part of this study, the psychometric properties reported are for paper and pencil versions of the questionnaires.
The BPI-SF 1 is a commonly used measure of pain intensity and pain interference.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  The SOT 13 assesses participants' attitudes towards their online administered treatment, and will be used at the study endline. Participants state how strongly they agree/disagree with each of the following items: (a) the use of a computer to access treatment, (b) level of easiness of the online intervention, (c) duration of the potential effects of the treatment, and (d) potential recommendation of online interventions to others. Responses range from "Agree very strongly" to "Disagree very strongly". An additional question asks participants how helpful they have found the online intervention, with responses ranging from "Very helpful" to "Not at all helpful".
Two open questions are also included that require participants to state the aspects of the intervention they most liked and disliked.
The EOT, developed by the researchers, will be presented at the end of every online session. The EOT includes three questions. The first asks participants to indicate where they

Supplementary Material 3 -Think Aloud Study
A qualitative think aloud study 1  Following the think-aloud interview, a short semi-structured interview took place for the researcher to ask questions about any specific aspects of the intervention that had not yet been discussed. Questions were also asked regarding thoughts about the intervention as a whole. This method of triangulation is commonly used to complement a think-aloud interview because it can be difficult to interpret spoken thoughts alone. 4 5 Following transcription of the interviews, thematic analysis using inductive encoding was used to identify themes that clearly represent the raw data, following guidelines set out by Braun and Clarke. 6 Three themes and 13 subthemes were identified, which are shown in a thematic map in Figure S1 and defined in Table S1 below. While it is beyond the scope of this article to present the results of this thematic analysis in full, the main points resulting in amendments to the iABMT intervention are presented here.
Regarding the iABMT website, participants liked the continuity of design between webpages, although pointed out inconsistencies in the formatting of text, which have been rectified. On some pages the volume of text was considered to be too great, and therefore where possible text has been reduced, language simplified, better use of spacing made, and longer paragraphs divided into multiple shorter paragraphs. While some participants were positive about the inclusion of images, others felt additional visual stimuli could be added throughout. It was therefore decided to only include images where these would help emphasize the points being made. Regarding the visual-probe task sessions, one important practicality raised was ability of participants to stay seated for a sufficient amount of time in order to complete the task in a single session. An additional inclusion criteria has therefore been added to the study, being that participants must be able to sit at a personal computer for forty minutes. It was also mentioned that participants needed sufficient computer skills to take part in the study. The inclusion criteria were therefore amended to state that participants need both access to and familiarity using a Window-based computer.     (iii) 18-session attentional modification group; or (iv) 18-session placebo training group. In the attentional modification groups, the visual-probe task will be used to implicitly train attention away from threatening information towards neutral information. Following the intervention, participants will complete a short interview exploring their perceptions about the online training.
In addition, a subgroup analysis for by participant age 16 -24 and 25 -60 will be undertaken.

Ethics and dissemination: This study has been approved by the University of Southampton
Research Ethics Committee. Results will be published in peer-reviewed journals, academic conferences, and in lay reports for pain charities and patient support groups. Registration: The study protocol has been registered with ClinicalTrial.gov (NCT02232100).

Strengths and limitations of this study
 This protocol describes an internet-delivered intervention to explore the efficacy of attentional bias modification training in patients with chronic musculoskeletal pain.
 Recruitment of a diverse sample in terms of age, socioeconomic status, and geographical region.
 Results will provide important information regarding dose effects, age effects and participants' experiences and attitudes using the online intervention.
 Limited control over the conditions under which training is completed.
 Impossibility of independently verifying participant diagnosis.

Introduction
Chronic musculoskeletal pain (CMSK) is pain arising from bones, muscles, ligaments, tendons and/or joints lasting for more than three months. 1 Prevalence estimates of CMSK vary considerably, which for adults is estimated to affect between 11.4 and 24% of the population 2 and for children and adolescents ranges between 4 and 40% of the population. 3 Negative effects on quality of life are commonly reported in adult 4-7 and paediatric [8][9][10][11] CMSK populations, and theory driven research [12][13][14] has shown that patients with chronic pain exhibit attentional biases (i.e., a selective attention) for salient pain-related words (e.g., [15][16][17][18] ) and images (e.g., 19 20   were found for pain, fear of pain, fear of re-injury, depression, anxiety, stress, anxiety sensitivity or pain self-efficacy. At 6-month follow-up (and after all participants had undergone 8 sessions of CBT) the ABM group, compared to the placebo group, showed significant improvements in disability and anxiety sensitivity, and marginally significant improvements in fear of re-injury.
No other significant effects were found, and the mechanism of action could not be established as ABM was not found to change patterns of attentional bias across time. Schoth and colleagues 27 reported statistically and clinically significant change pre-to post-ABM in pain intensity, pain interference, anxiety, and depression. Assessed via the McGill Pain Questionnaire 28 , significant changes pre-to post-ABM were shown for total pain, affective pain and miscellaneous pain, but not sensory-pain or evaluative pain. There was also no evidence that attentional biases changed across time.
One small RCT in adolescents with chronic pain randomised participants to either ABM, placebo training or waiting-list groups. No significant differences were found between the three groups in terms of pain, disability, pain catastrophising, anxiety, depression, or objective measures of physical functioning (sit-to-stand task and cardio wall tasks), and no evidence was found that ABM changed attentional bias or attentional control compared to placebo and waitinglist conditions. 29 Overall, while some studies have provided support for the benefits of ABM in adults, the evidence in regards to specific outcome variables is mixed and the mechanisms of action have yet to be established. Given the methodological shortcomings and small sample sizes of previous studies however, further research is needed to determine the therapeutic benefits of ABM for patients with chronic pain, along with the optimal form ABM should take and the impact of age on outcomes and intervention engagement. Considering the optimal form of ABM, a review of the broader cognitive bias modification (CBM) literature identified 12 published meta-analyses, 11 examining ABM specifically. 30 Three out of six analyses found the number of sessions to be a significant moderator of CBM, and three out of nine analyses found the number of sessions to be a significant moderator of symptom outcomes. Although evidence is therefore mixed, it is nevertheless worth exploring whether number of sessions impacts patterns of attentional bias and pain-related outcomes in individuals with chronic pain.
This article presents a study protocol for a randomised, double-blind internet-delivered ABM intervention. The results of a pilot think aloud study informing the design of the intervention are also presented. The aim of this RCT is to assess the efficacy of internetdelivered ABM in improving pain and pain-related distress in people aged 16 -60 with CMSK, and will report a subgroup by treatment effects using the two age brackets of 16-24 and 25-60.
While only limited evidence has been found for age as a moderator of CBM on bias change and symptoms, 30 it has been argued that the age of adolescence should be extended from 19 to 24 as the latter corresponds more closely to adolescent growth and popular understandings of this life phase. 31 Furthermore, although use of the internet has been growing among all age groups, there are nevertheless still some differences in internet use and activity according to age (e.g., in the UK 1% of those aged 16 to 24 do not use the internet, compared to 7% aged 45-54), 32 thus warranting a separate consideration of adolescent and adult participants. Overall, a diverse sample in terms of age, socioeconomic status, and geographical region will be recruited, thus increasing generalisability of results to the CMSK population. The primary outcome measure is pain interference. Secondary outcome measures are pain intensity, state and trait anxiety, depression, pain-related fear and sleep impairment, and engagement to and satisfaction with the online visual-probe training task. Dose effects will be explored via the inclusion of 10 versus 18 session conditions. It is hypothesised that participants in the intervention group, relative to those in the placebo group, will report significant reductions in pain interference, pain intensity, anxiety, depression, sleep impairment and pain-related fear at study endline. It is also hypothesised that dose will significantly moderate these findings, with greater effects in 18 compared to 10 sessions.

Participants
Participants will be recruited via press announcements, social media, and patient organizations throughout the UK. Inclusion criteria will be: (a) aged between 16 to 60 years old, (b) experiencing any type of CMSK (i.e., any condition that involves pain lasting for more than three months and arises from bones, muscles and/or joints), (c) able to sit at a personal computer

Patient and Public Involvement
Participant burden of the intervention and outcome measures were assessed using individual interviews and informal feedback from patients participating in two pilot studies. 27 33 Patients will not be involved in recruitment of participants or conduct of the study. Results of this study will be disseminated to participants through presentation at client and community forums.

Study Design and Setting
The study is a double-blind randomised controlled trial (RCT) with four arms exploring the efficacy of online ABM training versus a placebo training condition theorised to offer no specific therapeutic benefits. The choice of comparator was selected as placebo training closely mimics attentional bias modification training, and is frequently used as a comparator in ABM studies (e.g., 25 26 34 35 ). The study will take place in a location of the participant's choice (which we anticipate will typically be their home), which is accessed via personal computer connected to the internet.
The study design has a 2 x 2 x 3 experimental structure, with multiple non-commensurate dependent variables measuring pain intensity and interference, emotional functioning and painrelated disability. Treatment is a two-level factor (ABM, Placebo), number of Sessions is a twolevel factor (10 sessions, 18 sessions), with measures recorded at three points in time (baseline, endline, and 6-month follow-up). Measures in the 18 session groups (18AMG and 18 PTG) will also be taken after session 10.

Randomisation and Sample Size
Block randomisation of size four, performed via a randomisation command in the Lifeguide platform 36 , will be used to sequentially randomise eligible consecutive consenting participants to one of four groups: (i) 10-session attentional modification group (10AMG); (ii) 10-session placebo training group (10PTG); (iii) 18-session attentional modification group (18AMG); or (iv) 18-session placebo training group (18PTG). This blocked randomisation will be performed separately for those aged 16-24 and those aged 25-60. An allocation concealment mechanism will be used to ensure neither participants nor researchers know the study group to which the next participant will be assigned. This will be automatically performed within the Lifeguide platform (see below), with participants provided access to appropriate AMG or PTG sessions. Participants randomised to either 10-session condition will receive ten 35-minute online sessions across a four-week period, while those randomised to either 18-session condition will receive eighteen 35-minute online sessions across an eight-week period. All online sessions will be administered twice a week on a separate set of days (Monday-Thursday, Tuesday-Friday).
Participants randomised to either AMG condition will receive attentional training via the modified training version of the visual probe-task, while those randomised to either PTG condition will receive placebo training via the standard version of the visual-probe task. To maintain the overall quality and legitimacy of the intervention, code breaks (i.e., unblinding) will only occur in exceptional circumstances. Adherence will be monitored electronically via Lifeguide.
Our former lab-based proof-of-concept ABM intervention found reductions in pain intensity and pain interference pre-to post-ABM were associated with large effect sizes 27 , although differences in methodology including delivery (online vs lab-based) and number of sessions warrants a more conservative estimate. On this basis, the study will recruit a minimum of N = 100 with 1:1:1:1 randomisation. This study is powered primarily to establish treatment efficacy for the primary outcome variable of pain interference by considering baseline and measures after session 10 between those randomised to an attentional modification arm and those randomised to a placebo arm. Randomisation should ensure baseline comparability on measures between these two groups, and a difference in beneficial outcomes between these groups will be modelled using a linear mixed model. For an assumed correlation of 0.7 between baseline and end of session 10 measures a total of n = 40 per group (i.e. 20 per randomized arm) would be needed to detect small to moderate standardized intervention differences (Cohen's d = 0.25) with at least 80% power (alpha = 0.05, two-sided). The recruitment strategy includes a 20% oversampling to mitigate a loss of power from loss to follow-up

Procedure
Interested individuals will contact the researchers on the details provided in study advertisements and will be assessed against the inclusion and exclusion criteria via telephone interview. If eligible, they will receive a copy of the participant information sheet (PIS) detailing the requirements and procedure of the study, along with a link to the study website which provides further details on ABM and the research team. If the individual consents to take part they will be required to create an online ABM account. During registration, participants will select their preferred days for training, which will be either (i) Monday/Thursday or (ii) Tuesday/Friday. Session 1 is the baseline session, and includes the first assessment visual-probe task assessing attentional biases prior to beginning the intervention, along with the questionnaire battery assessing the primary and secondary outcome measures. Randomisation will take place following session 1, where participants will be informed of the length of their training (i.e., four or eight weeks). Participants randomised to either of the ten session conditions will complete four pictorial and four linguistic training sessions, while those randomised to either of the 18 session conditions will complete eight pictorial and eight linguistic training sessions (baseline and endline assessment sessions comprise the remainder of the 10/18 sessions). Participants' attentional biases will be re-assessed at endline (i.e., during the final session 10/18) using the same assessment version of the visual probe task (i.e., featuring the same stimuli) used at baseline and the same questionnaire battery. Participants randomised to either of the 18 session conditions will also have their attentional biases re-assessed in session 10 after their training session.
Participants' satisfaction with the online training will also be assessed. Six months after the last session, participants will be invited to again complete the online assessment visual-probe task (same as baseline and final session 10/18) and questionnaire battery. Within two weeks of the completion of the six-month follow-up session, participants will be invited to take part in a brief telephone semi-structured interview including 15 questions spread across five thematic sections: (a) motivation and expectations about the study, (b) experience of the online studyperson, environmental and lifestyle parameters, (c) experience of the visual-probe task, (d) understanding of the process of change, and (e) the visual-probe task as a potential therapeutic tool in pain management. The study flow is presented in Table 1.

MOS-SS
X X X

FOP-III
X X X SOT X Interview X T1 = Baseline phase including standard assessment visual-probe task and questionnaires. Also includes randomization to groups. T2 = Training phase including training visual-probe tasks. T3 = Evaluation phase including standard assessment visual-probe task and questionnaires. Participants randomized to 18 session conditions also complete evaluation phase during session 10. T4 = Six-month follow-up including standard assessment visual-probe task and questionnaires. T5 = Telephone interview within two weeks of T4. To retain as many participants as possible, reminder emails will be sent to participants 24 hours before each scheduled session becomes available, and also at 13:00 on the scheduled session date should the participant not have already logged into their iABMT account. An additional reminder email will be sent one week before their 6-month follow-up session is ready.
Participants will also be sent encouragement emails informing them when they have reach specific milestones (i.e., successfully completing 5 sessions for those randomised to complete 10 sessions; successfully completing 6 and 12 sessions for those randomised to 18 sessions).
Participants will also have the option of receiving an SMS message on their mobile phone at 09:00 on the morning of each scheduled session.

The Intervention
The intervention will be hosted using LifeGuide and iSurvey platforms, both developed by the University of Southampton.
LifeGuide is an open-source software which allows researchers to create online interventions. 36 iSurvey is a survey generation tool which allows researchers to create and disseminate questionnaires online. Participants will register for the intervention using LifeGuide, which will also host the majority of the questionnaires. iSurvey will be used to host the visual-probe tasks, along with the Engagement with Online Training questionnaire and the Brief Pain Inventory 37 that appear at the end of every visual-probe task session. The flow of sessions is provided in Figure 2, and examples of webpages are shown in Figure 3. On loading the intervention homepage, the individual is provided with a brief welcome to the website and rationale for the intervention. A recent review of cognitive bias meta-analyses concluded that effect sizes were smaller when biases were modified remotely compared to laboratory-based training. 30 We therefore decided to provide information on the rationale behind ABMT in order to increase motivation and reduce attrition as much as possible, which also mirrors clinical practice that involves educating patients into chronic pain and the psychological interventions used in its management. Individuals are able to either create an iABMT account or log into their existing account. Before any session participants are asked to indicate whether they  Participants are provided with guidance to ensure concentration and comfort is maintained neutral/neutral word pairs. Each task includes eight threatening words from each of the following categories: sensory-pain, affective-pain, health-threat and general-threat. Each pictorial task includes 32 threatening/neutral and 16 neutral/neutral image pairs. Each task includes eight threatening images from the following categories: musculoskeletal pain, facial expressions of pain, health-threat and general-threat. A total of 384 trials are included in each task, with each A separate linguistic visual-probe task will be used in the three assessment sessions, featuring different stimuli to the linguistic training visual-probe tasks. The use of separate assessment and training stimuli is necessary to establish whether training effects generalise to novel stimuli not used in the actual training. The same assessment stimuli will be used in all assessment sessions. The ABM training version of the visual-probe task to be completed by AMG groups includes three main stages per trial (Figure 1). Following a 500 ms initial fixation point, a stimulus pair are presented in distinct locations (e.g., above and below the initial fixation point) for either 500 or 1250 ms. The stimulus pair may be either words or images, although critically includes one threat-related and one neutral stimulus. 500 and 1250 ms stimuli presentation times are used as these are the most common stimuli presentation times adopted in chronic pain visual-probe studies (e.g., 18 20 47 ), and will allow us to closely compare our results to those of former research. Immediately following their presentation, the stimuli disappear and a probe appears (i.e., either 'p' or 'q') in the location of the neutral stimulus. Participants indicate the location of the probe as quickly and as accurately as possible via corresponding keys on their keyboard. In the standard version of this paradigm completed by PTG groups and used in the assessment sessions, the probe replaces the neutral and threat-related stimulus an equal number of times.

Outcome Measures
The primary outcome measure of pain interference will be assessed by the Brief Pain Inventory -Short Form (BPI-SF 37 ). Pain interference will be scored as the mean of seven interfernce items (i.e., general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Following guidance in the Brief Pain Inventory User Guide 48 and also IMMPACT recommendations for assessing pain in clinical trials, 49 we will include individual sessions, and at six-month follow-up. In the 18 session groups (18AMG and 18PTG) questionnaires will be administered to participants at baseline, after 10 sessions, after 18 sessions, and at six-month follow-up. At endline for each participant we will also assess whether the participant and researchers became aware at any point prior to endline which group they had been allocated to. Full details on each outcome measure are provided in Supplementary Material 2.

Think Aloud Study
A qualitative think aloud study 33 including a short semi-structured interview was conducted following the development of the initial version of the intervention with the aim to understand participants' first impressions and attitudes towards the intervention, and to collate feedback that could be used to make improvements. Details and outcomes of this study are provided in Supplementary Material 3.

Quantitative Analyses
A full and detailed Statistical Analysis Plan will be written prior to trial closure. In brief, the data analysis will be performed on an intention-to-treat (ITT) basis to provide an unbiased  55 Per protocol analyses will also be performed (comprising those correctly randomized, without protocol violations, and providing complete data on the primary outcome measure). Sweetman and Doig 56 have identified five types of protocol violations, including violations in (i) enrollment (i.e., failure to correctly apply eligibility criteria resulting in the enrolment of an inappropriate participant), (ii) randomization (i.e., violation of intended randomization sequence), (iii) study intervention (i.e., dosing, timing or delivery errors attributable to members of the research team), (iv) patient compliance (i.e., participants failing to comply with the trial protocol or other requirements of participation in the trial, such as skipping scheduled appointments or sessions), and (v) data collection (i.e., a failure by the research team to comply with pre-specific trial guidelines for data collection and/or outcome evaluation due to avoidable reasons). Any such violations will be clearly reported.
Analyses undertaken will include: (a) The primary analysis on pain interference will utilize the initial 2 by 2 by 2 structure comprising Stage (baseline, 10 weeks), randomized Treatment (AMBT, Placebo), and randomized number of Sessions (10,18). This comparison will be extended to compare 10AMG and 10PTG after 10 sessions, and to compare 18AMG and 18PTG after 10 sessions.
(c) An assessment of change in pain interference, both within and between groups, for 18AMG and 18PTG, between the end of session 10 and endline.
(d) The four randomized arms compared against one another on pain interference at each of baseline, after session 10, endline, and follow-up.  (16 -24; 25 -60) subgroup analysis using an age subgroup by treatment effect interaction. These analyses will be an extension of (a), (b), and (c) to incorporate age as a subgroup factor.
The same analyses would apply to the secondary outcome measures. The data will be represented descriptively and graphically by arm, and by treatment and age, and standardized effect sizes reported.
Linear mixed model with random intercepts will be used to analyze the data with, as appropriate, Treatment (AMBT, Placebo), number of Sessions (10, 18) and assessment stage as fixed factors. This approach avoids listwise deletion which would apply in a repeated measures ANOVA approach. The linear mixed modelling approach uses all of the available data and adheres to ITT. As a secondary analysis we will used multiple imputation chained equations (MICE) to impute outcome data 57 58 and use these imputed data sets in the linear mixed model.
Pairwise comparisons will follow the same procedure. An assessment of the sensitivity of findings to missing data mechanisms will be undertaken. 59 60 Specifically, we will use the strategy discussed by Morris and colleagues 60  Similar to former studies 25 27 the Reliable Change Index (RCI) 61 will be used to assess primary and secondary outcome measures for clinically significant changes. Here, a clinically significant result is a post-treatment score falling outside two standard deviations of the mean population of interest (in this study, two standard deviations outside pre-treatment means). In For visual-probe data, and as per former research 19 27 , practice and incorrect trials will be removed prior to analyses. Box and whisker plots for overall data will be used to reveal overall outliers, which will be removed. Following this, mean response times will be computed for each participant, with any response >3SD from their individual mean also removed as outliers. This process ensures extremely quick or slow responses do not unduly bias the results, which are typically removed when cleaning and screening visual-probe data in pain-related research (e.g., 18 63 64 65 66 ). An attentional bias index will then be computed for each stimulus and presentation time condition using the following equation: (TuPl − TlPl)+(TlPu −TuPu))/2. Here T is the threatening stimulus, P is the probe, u is the upper position, and l is the lower position. The attention capturing quality of threatening stimuli is measured by subtracting the mean probe detection time for congruent trials from the mean probe detection time of incongruent trials. 21 Split-half reliability will be computed via a bootstrap procedure, by randomly splitting the total number of trials in two halves, such that each half has the same number of congruent and incongruent trials. Attentional bias scores will be computed for each half and the correlation between them calculated across participants. This procedure will be repeated 100 times, and an average split-half correlation computed.

Qualitative Analyses
Qualitative analysis will be used to detail participants' experiences completing the iABMT intervention. Specifically, thematic analysis using inductive coding will be used to identify themes present in the data obtained from the semi-structured interviews and the two open-ended questions included in the Satisfaction with the Online Training questionnaire.
Guidelines provided by Braun and Clarke 67 will be followed. Following transcription of all interviews verbatim, initial codes will be generated. Potential themes and sub-themes will then be identified from the initial coding, which subsequently will be reviewed and refined. The validity of the themes in relation to the data set will also be considered. Each theme and subtheme will then be named and defined, and a thematic map of the data finalized. Examples from the data will be illustrated for each theme and sub-theme in the final report.

Ethics and Dissemination
This study has been approved by the University of Southampton Research Ethics Committee (ERGO ID: 26486), and the study protocol registered with ClinicalTrial.gov (NCT02232100). Ethical approval will be sought before any protocol modifications are made and the study protocol will be updated at ClinicalTrial.gov. Participants will provide informed consent prior to taking part in the study. All data will remain confidential and stored on password-protected systems and databases. Lifeguide and iSurvey servers both use HTTPS connections for security purposes. All data will be anonymised prior to dissemination, and personally identifiable information not known to anyone other than the researchers. Participants may withdraw from the intervention at any point by contacting the researchers via email or telephone, or by simply opting not to log into their iABMT account for their scheduled sessions.
Participants are also encouraged to contact the researchers should they experience any distress or discomfort completing the intervention. As per University policy, any adverse events, harms or complaints arising from participation in the intervention will be reported to the University of Southampton Research Governance Office. Findings will be published in the most relevant, high-impact peer-reviewed journals and presented at relevant conferences. Lay reports will be written for interested pain charities and patient support groups.             Linguistic visual-probe task

Session 10
Assessment visual-probe task and questionnaire battery Figure 2. Flow of the visual-probe task sessions for the 10-week and 18-week groups in the study.

Stimuli Development and Properties
A detailed description of the stimuli to be used in the iAMBT intervention is presented in this document. Linguistic stimulus properties and analyses on written frequency, valence, and arousal are first presented, followed by a description of pictorial stimuli properties and analyses of low-level features, valence, arousal and pain intensity. Following this, comparisons of stimuli properties between visual-probe sessions are then presented for linguistic and pictorial stimuli.

Linguistic stimuli
Properties. Linguistic and pictorial versions of the visual-probe task will be used. Each linguistic visual-probe task will include 32 threatening/neutral and 16 neutral/neutral word pairs.
Threatening words stem from the following categories, with 8 words from each included in each visual-probe task: (i) sensory-pain words reflecting the sensory dimension of pain (e.g., shooting; burning; aching); (ii) affective-pain words reflecting the unpleasantness of pain and negative emotions associated with pain (e.g., hopeless, punishing, tormenting); (iii) health-threat words reflecting threat to health and well-being (e.g., hospital, doctor, stress); and (iv) general-threat words reflecting physical and emotional sources of threat, including manmade threat (e.g., gun), natural threat (e.g., fire), social threat (e.g., humiliation), and emotional threat (e.g., sad). Neutral words (including the neutral counterparts of the threatening words) include non-threatening words unrelated to pain or suffering (e.g., version; rector; monument), which were matched with their threatening counterparts on Kucera-Francis written frequency of use in the English language 1 and word length. Matching on written frequency minimise the chances of participants preferentially processing one stimulus due to its high frequency of use (e.g., faster recognition) when displayed simultaneously with another stimulus 2 3 , while matching word length also minimise the chances of participants attending towards a stimulus due to its size.
In total, 864 words have been collected from previous studies exploring and modifying biases in pain and/or anxiety (i.e., [4][5][6][7][8], including words from the McGill Pain Questionnaire. 9  10 , an online psycholinguistic tool that generates words with specific lexical characteristics. The database includes a dictionary of 150,837 English words providing syntactic, semantic and orthographical properties of each word. 11 Valence and arousal can influence attentional allocation to external stimuli. 12 13 A computerised version of the SAM task 14 was therefore used to collect ratings on valence and arousal for each word in a sample of sixteen healthy, pain-free participants (Mage = 25.9, SD = 4.08, range: 20 -33 years; 8 female). All words were randomly presented to participants for 3 seconds each. Following each word, two 9point SAM scales were presented, one for valence (1 = low pleasure to 9 = high pleasure) and one for arousal (1 = low arousal to 9 = high arousal). As per former chronic pain attentional bias research (e.g., 5 15 16 ), stimuli categories were assessed but not matched on valence and arousal, as differences are expected to exist between categories.

Analyses and results: written frequency, valence, and arousal. Analyses comparing
properties between the five word categories are presented here, while analyses comparing word properties between the nine linguistic visual-probe tasks are presented below. One-way ANOVA was conducted comparing Kucera-Francis written frequency (     This rating aimed to assess the degree to which images included in the pain-related categories were perceived as depicting pain. Sixteen healthy, pain-free participants (Mage = 24.8, SD = 4.56, range: 20 -33 years; 8 female) were recruited to provide ratings on valence, arousal, and pain intensity (this was a separate sample to that recruited to provide linguistic stimuli ratings).
Analyses and results: Low-level features. Analyses comparing properties between the five image categories on low-level features (Table 3) are presented here, while analyses   (Table 4) (Table 4)  An independent samples t-test was conducted comparing pain intensity scores (Table 4) between the images in the musculoskeletal pain and facial expressions of pain categories. There

Post-hoc analyses across sessions.
To explore the significant interaction, a series of oneway ANOVAS with 9 levels (Session; 1, 3,5,7,9,11,13,15,17) were run for each word category independently. These explored whether the pleasantness ratings for each word category differed across the sessions. For the sensory-pain words, a main effect of session was found,   For session 9, a significant main effect was found, F(2,31) = 13.67, p < .001, p 2 = .48.
Pairwise comparisons revealed that the sensory-pain words were significantly more pleasant than For session 11, a significant main effect was found, F(3,45) = 11.63, p < .001, p 2 = .44.
Pairwise comparisons revealed that the sensory-pain words were significantly more pleasant than

Supplementary Material 2 -Outcome Measures
A detailed description of each outcome measure used in this study is provided here.
While the questionnaires will be administered online as part of this study, the psychometric properties reported are for paper and pencil versions of the questionnaires.
The BPI-SF 1 is a commonly used measure of pain intensity and pain interference. The FOP-III 8 is a 30 item measure of pain-related fear. On a 5-point scale, respondents are asked to rate how fearful they are of pain associated with specific situations and events (e.g., being in an automobile accident). Possible scores range between 30 and 150, with higher scores representing a more intense fear of pain. In addition to a total score, the measure also provides subscales of minor, severe, and medical pain-related fear. The FOP-III is commonly used in clinical and non-clinical populations, and possesses high internal consistency as indexed in a nonclinical sample (total score = .93; severe = .88; minor = .86, medical = .88). 9 The MOS-SS 10 is a twelve-item questionnaire developed for patients with chronic illness, measuring six dimensions of sleep over the past four weeks; sleep initiation (time to fall asleep), quantity (hours per night sleeping), maintenance, respiratory problems, perceived adequacy, and somnolence. A sleep problems index which summarises information from nine items may also be scored. Responses are recoded on a 0 -100 scale, with higher scores indicating more of the concept being measured (e.g., greater difficulties falling asleep). Research has supported the internal consistency of the MOS-SS scales to be acceptable (.70) or higher in samples of patients with neuropathic pain. 11 12 The SOT 13 assesses participants' attitudes towards their online administered treatment, and will be used at the study endline. Participants state how strongly they agree/disagree with each of the following items: (a) the use of a computer to access treatment, (b) level of easiness of the online intervention, (c) duration of the potential effects of the treatment, and (d) potential recommendation of online interventions to others. Responses range from "Agree very strongly" to "Disagree very strongly". An additional question asks participants how helpful they have found the online intervention, with responses ranging from "Very helpful" to "Not at all helpful".
Two open questions are also included that require participants to state the aspects of the intervention they most liked and disliked.

Supplementary Material 3 -Think Aloud Study
A qualitative think aloud study 1  Following the think-aloud interview, a short semi-structured interview took place for the researcher to ask questions about any specific aspects of the intervention that had not yet been discussed. Questions were also asked regarding thoughts about the intervention as a whole. This method of triangulation is commonly used to complement a think-aloud interview because it can be difficult to interpret spoken thoughts alone. 4 5 Following transcription of the interviews, thematic analysis using inductive encoding was used to identify themes that clearly represent the raw data, following guidelines set out by Braun and  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Clarke. 6 Three themes and 13 subthemes were identified, which are shown in a thematic map in Figure S1 and defined in Table S1 below. While it is beyond the scope of this article to present the results of this thematic analysis in full, the main points resulting in amendments to the iABMT intervention are presented here.
Regarding the iABMT website, participants liked the continuity of design between webpages, although pointed out inconsistencies in the formatting of text, which have been rectified. On some pages the volume of text was considered to be too great, and therefore where possible text has been reduced, language simplified, better use of spacing made, and longer paragraphs divided into multiple shorter paragraphs. While some participants were positive about the inclusion of images, others felt additional visual stimuli could be added throughout. It was therefore decided to only include images where these would help emphasize the points being made. Regarding the visual-probe task sessions, one important practicality raised was ability of participants to stay seated for a sufficient amount of time in order to complete the task in a single session. An additional inclusion criteria has therefore been added to the study, being that participants must be able to sit at a personal computer for forty minutes. It was also mentioned that participants needed sufficient computer skills to take part in the study. The inclusion criteria were therefore amended to state that participants need both access to and familiarity using a Window-based computer.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59   Names, affiliations, and roles of protocol contributors 1, 28 Roles and responsibilities 5b Name and contact information for the trial sponsor 28 5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities 28 5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee) _____________  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory) 7-8

Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained 6-8 Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists) 7 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be administered 8-14 11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

19
11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

13
Interventions 11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 7 Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

Methods: Assignment of interventions (for controlled trials)
Allocation: Sequence generation 16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions 8-9 Allocation concealment mechanism 16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned 8-9 Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions 8-9 Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how 8-9 17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant's allocated intervention during the trial 8-9 Methods: Data collection, management, and analysis

Data collection methods 18a
Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol 19 Statistical methods 20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol 15-19 20b Methods for any additional analyses (eg, subgroup and adjusted analyses) 17

11-12
20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) 17

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed _____________ 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial _____________ Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct 19 Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor _____________  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial 19

Declaration of interests 28
Financial and other competing interests for principal investigators for the overall trial and each study site 28 Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators    1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Participants with chronic musculoskeletal pain will be randomised to one of four groups: (i) 10session attentional modification group; (ii) 10-session placebo training group; (iii) 18-session attentional modification group; or (iv) 18-session placebo training group. In the attentional modification groups, the probe-classification version of the visual-probe task will be used to implicitly train attention away from threatening information towards neutral information.
Following the intervention, participants will complete a short interview exploring their perceptions about the online training. In addition, a subgroup analysis for by participant age 16 -24 and 25 -60 will be undertaken. Ethics and dissemination: This study has been approved by the University of Southampton Research Ethics Committee. Results will be published in peerreviewed journals, academic conferences, and in lay reports for pain charities and patient support groups. Registration: The study protocol has been registered with ClinicalTrial.gov (NCT02232100).

Strengths and limitations of this study
 This protocol describes an internet-delivered intervention to explore the efficacy of attentional bias modification training in patients with chronic musculoskeletal pain.
 Recruitment of a diverse sample in terms of age, socioeconomic status, and geographical region.
 Results will provide important information regarding dose effects, age effects and participants' experiences and attitudes using the online intervention.
 Limited control over the conditions under which training is completed.
 Impossibility of independently verifying participant diagnosis.

Introduction
Chronic musculoskeletal pain (CMSK) is pain arising from bones, muscles, ligaments, tendons and/or joints lasting for more than three months. 1 Prevalence estimates of CMSK vary considerably, which for adults is estimated to affect between 11.4 and 24% of the population 2 and for children and adolescents ranges between 4 and 40% of the population. 3 Negative effects on quality of life are commonly reported in adult 4-7 and paediatric [8][9][10][11] CMSK populations, and theory driven research [12][13][14] has shown that patients with chronic pain exhibit attentional biases (i.e., a selective attention) for salient pain-related words (e.g., [15][16][17][18] ) and images (e.g., 19 20 )    for total pain, affective pain and miscellaneous pain, but not sensory-pain or evaluative pain.
There was also no evidence that attentional biases changed across time.
One small RCT in adolescents with chronic pain randomised participants to either ABM, placebo training or waiting-list groups. No significant differences were found between the three groups in terms of pain, disability, pain catastrophising, anxiety, depression, or objective measures of physical functioning (sit-to-stand task and cardio wall tasks), and no evidence was found that ABM changed attentional bias or attentional control compared to placebo and waitinglist conditions. 29 Overall, while some studies have provided support for the benefits of ABM in adults, the evidence in regards to specific outcome variables is mixed and the mechanisms of action have yet to be established. Given the methodological shortcomings and small sample sizes of previous studies however, further research is needed to determine the therapeutic benefits of ABM for patients with chronic pain, along with the optimal form ABM should take and the impact of age on outcomes and intervention engagement. Considering the optimal form of ABM, a review of the broader cognitive bias modification (CBM) literature identified 12 published meta-analyses, 11 examining ABM specifically. 30 Three out of six analyses found the number of sessions to be a significant moderator of CBM, and three out of nine analyses found the number of sessions to be a significant moderator of symptom outcomes. Although evidence is therefore mixed, it is nevertheless worth exploring whether number of sessions impacts patterns of attentional bias and pain-related outcomes in individuals with chronic pain.
This article presents a study protocol for a randomised, double-blind internet-delivered ABM intervention. The results of a pilot think aloud study informing the design of the intervention are also presented. The aim of this RCT is to assess the efficacy of internetdelivered ABM in improving pain and pain-related distress in people aged 16 -60 with CMSK, and will report a subgroup by treatment effects using the two age brackets of 16-24 and 25-60.
While only limited evidence has been found for age as a moderator of CBM on bias change and symptoms, 30 it has been argued that the age of adolescence should be extended from 19 to 24 as the latter corresponds more closely to adolescent growth and popular understandings of this life phase. 31 Furthermore, although use of the internet has been growing among all age groups, there are nevertheless still some differences in internet use and activity according to age (e.g., in the UK 1% of those aged 16 to 24 do not use the internet, compared to 7% aged 45-54), 32 thus warranting a separate consideration of adolescent and adult participants. Overall, a diverse sample in terms of age, socioeconomic status, and geographical region will be recruited, thus increasing generalisability of results to the CMSK population. The primary outcome measure is pain interference. Secondary outcome measures are pain intensity, state and trait anxiety, depression, pain-related fear and sleep impairment, and engagement to and satisfaction with the online visual-probe training task. Dose effects will be explored via the inclusion of 10 versus 18 session conditions. It is hypothesised that participants in the intervention group, relative to those in the placebo group, will report significant reductions in pain interference, pain intensity, anxiety, depression, sleep impairment and pain-related fear at study endline. It is also hypothesised that dose will significantly moderate these findings, with greater effects in 18 compared to 10 sessions.

Participants
Participants will be recruited via press announcements, social media, and patient organizations throughout the UK. Inclusion criteria will be: (a) aged between 16 to 60 years old, (b) experiencing any type of CMSK (i.e., any condition that involves pain lasting for more than three months and arises from bones, muscles and/or joints), (c) able to sit at a personal computer

Patient and Public Involvement
Participant burden of the intervention and outcome measures were assessed using individual interviews and informal feedback from patients participating in two pilot studies. 27 33 Patients will not be involved in recruitment of participants or conduct of the study. Results of this study will be disseminated to participants through presentation at client and community forums.

Study Design and Setting
The study is a double-blind randomised controlled trial (RCT) with four arms exploring the efficacy of online ABM training versus a placebo training condition theorised to offer no specific therapeutic benefits. The choice of comparator was selected as placebo training closely mimics attentional bias modification training, and is frequently used as a comparator in ABM studies (e.g., 25 26 34 35 ). The study will take place in a location of the participant's choice (which we anticipate will typically be their home), which is accessed via personal computer connected to the internet.
The study design has a 2 x 2 x 3 experimental structure, with multiple non-commensurate dependent variables measuring pain intensity and interference, emotional functioning and painrelated disability. Treatment is a two-level factor (ABM, Placebo), number of Sessions is a twolevel factor (10 sessions, 18 sessions), with measures recorded at three points in time (baseline, endline, and 6-month follow-up). Measures in the 18 session groups (18AMG and 18 PTG) will also be taken after session 10.

Randomisation and Sample Size
Block randomisation of size four, performed via a randomisation command in the Lifeguide platform 36 , will be used to sequentially randomise eligible consecutive consenting participants to one of four groups: (i) 10-session attentional modification group (10AMG); (ii) 10-session placebo training group (10PTG); (iii) 18-session attentional modification group (18AMG); or (iv) 18-session placebo training group (18PTG). This blocked randomisation will be performed separately for those aged 16-24 and those aged 25-60. An allocation concealment mechanism will be used to ensure neither participants nor researchers know the study group to which the next participant will be assigned. This will be automatically performed within the Lifeguide platform (see below), with participants provided access to appropriate AMG or PTG sessions. Participants randomised to either 10-session condition will receive ten 35-minute online sessions across a four-week period, while those randomised to either 18-session condition will receive eighteen 35-minute online sessions across an eight-week period. All online sessions will be administered twice a week on a separate set of days (Monday-Thursday, Tuesday-Friday).
Participants randomised to either AMG condition will receive attentional training via the modified training version of the probe-classification visual probe-task, while those randomised to either PTG condition will receive placebo training via the standard version of the probeclassification visual-probe task. To maintain the overall quality and legitimacy of the intervention, code breaks (i.e., unblinding) will only occur in exceptional circumstances.
Adherence will be monitored electronically via Lifeguide.
Our former lab-based proof-of-concept ABM intervention found reductions in pain intensity and pain interference pre-to post-ABM were associated with large effect sizes 27 , although differences in methodology including delivery (online vs lab-based) and number of sessions warrants a more conservative estimate. On this basis, the study will recruit a minimum of N = 100 with 1:1:1:1 randomisation. This study is powered primarily to establish treatment efficacy for the primary outcome variable of pain interference by considering baseline and measures after session 10 between those randomised to an attentional modification arm and those randomised to a placebo arm. Randomisation should ensure baseline comparability on measures between these two groups, and a difference in beneficial outcomes between these groups will be modelled using a linear mixed model. For an assumed correlation of 0.7 between baseline and end of session 10 measures a total of n = 40 per group (i.e. 20 per randomized arm) would be needed to detect small to moderate standardized intervention differences (Cohen's d = 0.25) with at least 80% power (alpha = 0.05, two-sided). The recruitment strategy includes a 20% oversampling to mitigate a loss of power from loss to follow-up

Procedure
Interested individuals will contact the researchers on the details provided in study advertisements and will be assessed against the inclusion and exclusion criteria via telephone interview. If eligible, they will receive a copy of the participant information sheet (PIS) detailing the requirements and procedure of the study, along with a link to the study website which provides further details on ABM and the research team. If the individual consents to take part they will be required to create an online ABM account. During registration, participants will select their preferred days for training, which will be either (i) Monday/Thursday or (ii) Tuesday/Friday.   Table 1.  To retain as many participants as possible, reminder emails will be sent to participants 24 hours before each scheduled session becomes available, and also at 13:00 on the scheduled session date should the participant not have already logged into their iABMT account. An additional reminder email will be sent one week before their 6-month follow-up session is ready.
Participants will also be sent encouragement emails informing them when they have reach specific milestones (i.e., successfully completing 5 sessions for those randomised to complete 10 sessions; successfully completing 6 and 12 sessions for those randomised to 18 sessions).
Participants will also have the option of receiving an SMS message on their mobile phone at 09:00 on the morning of each scheduled session.

The Intervention
The intervention will be hosted using LifeGuide and iSurvey platforms, both developed by the University of Southampton.
LifeGuide is an open-source software which allows researchers to create online interventions. 36 iSurvey is a survey generation tool which allows researchers to create and disseminate questionnaires online. Participants will register for the intervention using LifeGuide, which will also host the majority of the questionnaires. iSurvey will be used to host the visual-probe tasks, along with the Engagement with Online Training questionnaire and the Brief Pain Inventory 37 that appear at the end of every visual-probe task session. The flow of sessions is provided in Figure 2, and examples of webpages are shown in Figure 3. On loading the intervention homepage, the individual is provided with a brief welcome to the website and rationale for the intervention. A recent review of cognitive bias meta-analyses concluded that effect sizes were smaller when biases were modified remotely compared to laboratory-based training. 30 We therefore decided to provide information on the rationale behind ABMT in order to increase motivation and reduce attrition as much as possible, which also Participants are provided with guidance to ensure concentration and comfort is maintained  A separate linguistic visual-probe task will be used in the three assessment sessions, featuring different stimuli to the linguistic training visual-probe tasks. The use of separate assessment and training stimuli is necessary to establish whether training effects generalise to novel stimuli not used in the actual training. The same assessment stimuli will be used in all assessment sessions. The ABM training version of the visual-probe task to be completed by AMG groups includes three main stages per trial (Figure 1). Following a 500 ms initial fixation point, a stimulus pair are presented in distinct locations (e.g., above and below the initial fixation point) for either 500 or 1250 ms. The stimulus pair may be either words or images, although critically includes one threat-related and one neutral stimulus. 500 and 1250 ms stimuli presentation times are used as these are the most common stimuli presentation times adopted in chronic pain visual-probe studies (e.g., 18 20 47 ), and will allow us to closely compare our results to those of former research. Immediately following their presentation, the stimuli disappear and a probe appears (either 'p' or 'q') in the location of the neutral stimulus. Participants use corresponding keys on their keyboard to indicate the probe letter as quickly and as accurately as possible. In the standard version of this paradigm completed by PTG groups and used in the assessment sessions, the probe replaces the neutral and threat-related stimulus an equal number of times. The probe-classification version of the visual-prove task is argued to encourage a more even monitoring of the display than the probe-position version (i.e., which requires participants to indicate the location of a dot, either left/right or up/down), as for the latter participants can adopt biased monitoring strategies favouring one particular region over the other. 48 As any such biases in monitoring many affect training, we will use the probe-classification version of the visualprobe task. session groups (10AMG and 10PTG) will be administered to participants at baseline, after 10 sessions, and at six-month follow-up. In the 18 session groups (18AMG and 18PTG) questionnaires will be administered to participants at baseline, after 10 sessions, after 18 sessions, and at six-month follow-up. At endline for each participant we will also assess whether the participant and researchers became aware at any point prior to endline which group they had been allocated to. Full details on each outcome measure are provided in Supplementary Material 2.

Think Aloud Study
A qualitative think aloud study 33 including a short semi-structured interview was conducted following the development of the initial version of the intervention with the aim to understand participants' first impressions and attitudes towards the intervention, and to collate

Quantitative Analyses
A full and detailed Statistical Analysis Plan will be written prior to trial closure. In brief, the data analysis will be performed on an intention-to-treat (ITT) basis to provide an unbiased estimate of the treatment effect. 56 Per protocol analyses will also be performed (comprising those correctly randomized, without protocol violations, and providing complete data on the primary outcome measure). Sweetman and Doig 57 have identified five types of protocol violations, including violations in (i) enrollment (i.e., failure to correctly apply eligibility criteria resulting in the enrolment of an inappropriate participant), (ii) randomization (i.e., violation of intended randomization sequence), (iii) study intervention (i.e., dosing, timing or delivery errors attributable to members of the research team), (iv) patient compliance (i.e., participants failing to comply with the trial protocol or other requirements of participation in the trial, such as skipping scheduled appointments or sessions), and (v) data collection (i.e., a failure by the research team to comply with pre-specific trial guidelines for data collection and/or outcome evaluation due to avoidable reasons). Any such violations will be clearly reported.
Analyses undertaken will include: (a) The primary analysis on pain interference will utilize the initial 2 by 2 by 2 structure comprising Stage (baseline, 10 weeks), randomized Treatment (AMBT, Placebo), and randomized number of Sessions (10,18). This comparison will be extended to compare 10AMG and 10PTG after 10 sessions, and to compare 18AMG and 18PTG after 10 sessions.
(b) An analysis of pain interference will utilize the 2 by 2 by 3 structure comprising randomised Treatment (AMBT, Placebo), randomized number of Sessions (10,18), and Stage (baseline, endline, follow-up). (c) An assessment of change in pain interference, both within and between groups, for 18AMG and 18PTG, between the end of session 10 and endline.
(d) The four randomized arms compared against one another on pain interference at each of baseline, after session 10, endline, and follow-up.
(e) An age (16 -24; 25 -60) subgroup analysis using an age subgroup by treatment effect interaction. These analyses will be an extension of (a), (b), and (c) to incorporate age as a subgroup factor.
The same analyses would apply to the secondary outcome measures. The data will be represented descriptively and graphically by arm, and by treatment and age, and standardized effect sizes reported.
Linear mixed model with random intercepts will be used to analyze the data with, as appropriate, Treatment (AMBT, Placebo), number of Sessions (10,18) and assessment stage as fixed factors. This approach avoids listwise deletion which would apply in a repeated measures ANOVA approach. The linear mixed modelling approach uses all of the available data and adheres to ITT. As a secondary analysis we will used multiple imputation chained equations (MICE) to impute outcome data 58 59 and use these imputed data sets in the linear mixed model.
Pairwise comparisons will follow the same procedure. An assessment of the sensitivity of findings to missing data mechanisms will be undertaken. 60   For visual-probe data, and as per former research 19 27 , practice and incorrect trials will be removed prior to analyses. Box and whisker plots for overall data will be used to reveal overall outliers, which will be removed. Following this, mean response times will be computed for each participant, with any response >3SD from their individual mean also removed as outliers. This process ensures extremely quick or slow responses do not unduly bias the results, which are typically removed when cleaning and screening visual-probe data in pain-related research (e.g., 18 64 65 66 67 ). An attentional bias index will then be computed for each stimulus and presentation time condition using the following equation: (TuPl − TlPl)+(TlPu −TuPu))/2. Here T is the threatening stimulus, P is the probe, u is the upper position, and l is the lower position. The attention capturing quality of threatening stimuli is measured by subtracting the mean probe classification time for congruent trials from the mean probe classification time of incongruent trials. 21 Split-half reliability will be computed via a bootstrap procedure, by randomly splitting the total number of trials in two halves, such that each half has the same number of congruent and incongruent trials. Attentional bias scores will be computed for each half and the correlation between them calculated across participants. This procedure will be repeated 100 times, and an average split-half correlation computed.

Qualitative Analyses
Qualitative analysis will be used to detail participants' experiences completing the iABMT intervention. Specifically, thematic analysis using inductive coding will be used to Guidelines provided by Braun and Clarke 68 will be followed. Following transcription of all interviews verbatim, initial codes will be generated. Potential themes and sub-themes will then be identified from the initial coding, which subsequently will be reviewed and refined. The validity of the themes in relation to the data set will also be considered. Each theme and subtheme will then be named and defined, and a thematic map of the data finalized. Examples from the data will be illustrated for each theme and sub-theme in the final report.

Stimuli Development and Properties
A detailed description of the stimuli to be used in the iAMBT intervention is presented in this document. Linguistic stimulus properties and analyses on written frequency, valence, and arousal are first presented, followed by a description of pictorial stimuli properties and analyses of low-level features, valence, arousal and pain intensity. Following this, comparisons of stimuli properties between visual-probe sessions are then presented for linguistic and pictorial stimuli.

Linguistic stimuli
Properties. Linguistic and pictorial versions of the visual-probe task will be used. Each linguistic visual-probe task will include 32 threatening/neutral and 16 neutral/neutral word pairs.
Threatening words stem from the following categories, with 8 words from each included in each visual-probe task: (i) sensory-pain words reflecting the sensory dimension of pain (e.g., shooting; burning; aching); (ii) affective-pain words reflecting the unpleasantness of pain and negative emotions associated with pain (e.g., hopeless, punishing, tormenting); (iii) health-threat words reflecting threat to health and well-being (e.g., hospital, doctor, stress); and (iv) general-threat words reflecting physical and emotional sources of threat, including manmade threat (e.g., gun), natural threat (e.g., fire), social threat (e.g., humiliation), and emotional threat (e.g., sad). Neutral words (including the neutral counterparts of the threatening words) include non-threatening words unrelated to pain or suffering (e.g., version; rector; monument), which were matched with their threatening counterparts on Kucera-Francis written frequency of use in the English language 1 and word length. Matching on written frequency minimise the chances of participants preferentially processing one stimulus due to its high frequency of use (e.g., faster recognition) when displayed simultaneously with another stimulus 2 3 , while matching word length also minimise the chances of participants attending towards a stimulus due to its size.

Supplementary Material 2 -Outcome Measures
A detailed description of each outcome measure used in this study is provided here.
While the questionnaires will be administered online as part of this study, the psychometric properties reported are for paper and pencil versions of the questionnaires.
The BPI-SF 1 is a commonly used measure of pain intensity and pain interference.  The FOP-III 8 is a 30 item measure of pain-related fear. On a 5-point scale, respondents are asked to rate how fearful they are of pain associated with specific situations and events (e.g., being in an automobile accident). Possible scores range between 30 and 150, with higher scores representing a more intense fear of pain. In addition to a total score, the measure also provides subscales of minor, severe, and medical pain-related fear. The FOP-III is commonly used in clinical and non-clinical populations, and possesses high internal consistency as indexed in a nonclinical sample (total score = .93; severe = .88; minor = .86, medical = .88). 9 The MOS-SS 10 is a twelve-item questionnaire developed for patients with chronic illness, measuring six dimensions of sleep over the past four weeks; sleep initiation (time to fall asleep), quantity (hours per night sleeping), maintenance, respiratory problems, perceived adequacy, and somnolence. A sleep problems index which summarises information from nine items may also be scored. Responses are recoded on a 0 -100 scale, with higher scores indicating more of the concept being measured (e.g., greater difficulties falling asleep). Research has supported the internal consistency of the MOS-SS scales to be acceptable (.70) or higher in samples of patients with neuropathic pain. 11 12 The SOT 13 assesses participants' attitudes towards their online administered treatment, and will be used at the study endline. Participants state how strongly they agree/disagree with each of the following items: (a) the use of a computer to access treatment, (b) level of easiness of the online intervention, (c) duration of the potential effects of the treatment, and (d) potential recommendation of online interventions to others. Responses range from "Agree very strongly" to "Disagree very strongly". An additional question asks participants how helpful they have found the online intervention, with responses ranging from "Very helpful" to "Not at all helpful".
Two open questions are also included that require participants to state the aspects of the intervention they most liked and disliked.
The EOT, developed by the researchers, will be presented at the end of every online session. The EOT includes three questions. The first asks participants to indicate where they completed the online training session (e.g., home or office). The second is related to whether or not they have been distracted during the training and, if distracted, to indicate the source of distraction (e.g., telephone ringing). The third question asks participants to rate the level of their concentration during the online task on an 11-point Visual Analogue Scale (VAS) numbered from 0 (i.e., no concentration at all) to 10 (i.e. very concentrated).

Supplementary Material 3 -Think Aloud Study
A qualitative think aloud study 1  Following the think-aloud interview, a short semi-structured interview took place for the researcher to ask questions about any specific aspects of the intervention that had not yet been discussed. Questions were also asked regarding thoughts about the intervention as a whole. This method of triangulation is commonly used to complement a think-aloud interview because it can be difficult to interpret spoken thoughts alone. 4 5 Following transcription of the interviews, thematic analysis using inductive encoding was used to identify themes that clearly represent the raw data, following guidelines set out by Braun and Clarke. 6 Three themes and 13 subthemes were identified, which are shown in a thematic map in Figure S1 and defined in Table S1 below. While it is beyond the scope of this article to present the results of this thematic analysis in full, the main points resulting in amendments to the iABMT intervention are presented here.
Regarding the iABMT website, participants liked the continuity of design between webpages, although pointed out inconsistencies in the formatting of text, which have been rectified. On some pages the volume of text was considered to be too great, and therefore where possible text has been reduced, language simplified, better use of spacing made, and longer paragraphs divided into multiple shorter paragraphs. While some participants were positive about the inclusion of images, others felt additional visual stimuli could be added throughout. It was therefore decided to only include images where these would help emphasize the points being made. Regarding the visual-probe task sessions, one important practicality raised was ability of participants to stay seated for a sufficient amount of time in order to complete the task in a single session. An additional inclusion criteria has therefore been added to the study, being that participants must be able to sit at a personal computer for forty minutes. It was also mentioned that participants needed sufficient computer skills to take part in the study. The inclusion criteria were therefore amended to state that participants need both access to and familiarity using a Window-based computer.  Names, affiliations, and roles of protocol contributors 1, 28 Roles and responsibilities 5b Name and contact information for the trial sponsor 28 5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities 28 5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee) _____________ Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory) 7-8

Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained 6-8 Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists) 7 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be administered 8-14 11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

19
11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

13
Interventions 11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 7 Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

14-15
Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure) Table

Methods: Assignment of interventions (for controlled trials)
Allocation: Sequence generation 16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions 8-9 Allocation concealment mechanism 16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned 8-9 Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions 8-9 Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how 8-9 17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant's allocated intervention during the trial 8-9 Methods: Data collection, management, and analysis

Data collection methods 18a
Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol 15-19, Supplementary material 2 18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols  Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol 19 Statistical methods 20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol 15-19 20b Methods for any additional analyses (eg, subgroup and adjusted analyses) 17

11-12
20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) 17

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed _____________ 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial _____________ Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct 19 Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor _____________ How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial 19 Declaration of interests 28 Financial and other competing interests for principal investigators for the overall trial and each study site 28